A survey to investigate the association of pain, foot disability and quality of life with corns

Background Corns are a common foot problem affecting a large proportion of the population. This study describes the characteristics of corns experienced by 201 participants taking part in a randomised controlled trial to investigate associations between demographic and corn parameters on pain, foot related disability and quality of life (QoL). Methods Pain from the main (index) corn was measured using a visual analogue scale (VAS); foot related disability was assessed with the Foot Disability Questionnaire (now known as the Manchester Foot Pain and Disability Index) and quality of life was recorded with the EQ-5D questionnaire. The effect of demographic and corn parameters on the pain and quality of life outcomes was assessed with analysis of variance (ANOVA) methods. The effect of the same factors on a linear combination of the foot-related disability outcome measures was assessed using multivariate ANOVA methods. Pain was also tested for its mediating properties on the causal pathway between the independent variables and quality of life. Results The mean pain score was 5.29 points on a 10 cm VAS, with females reporting substantively higher pain levels than males. Age affected foot-related disability, with lower levels on all domains of the MFPDI reported in older participants; each year of advancing age was associated with falls of: 0.009 points on the Concern about Appearance (CA) domain; 0.047 points on the Functional Limitation (FL) domain and 0.048 points on the Pain Intensity (PI) domain. Sex and corn type also affected disability, with higher scores reported by females and participants with plantar corns. Conclusions The effect of pain was shown to mediate the relationship between sex and foot-related disability. The presence of plantar corns has a more detrimental effect on QoL than dorsal/inter-digital corns

Renal cell carcinoma metastasis to the ciliary body responds to proton beam radiotherapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report an unexpected presentation of metastatic renal cell carcinoma (RCC) to the ciliary body and an interesting response to proton beam radiotherapy.</p> <p>Case presentation</p> <p>We encountered a case of angle-closure glaucoma as the initial presentation of ocular metastasis to the ciliary body in a 65-year-old Caucasian man who had undergone right radical nephrectomy for RCC 15 years earlier. He underwent YAG (yttrium aluminium garnet) laser peripheral iridotomy while further metastatic workup took place. His condition was eventually diagnosed as stage IV metastatic RCC of the clear cell type and involved multiple sites, including the ciliary body, brain, lungs, liver, and pancreas. The progression of RCC metastasis to the ciliary body was studied for 16 months. The ciliary body mass continued to grow despite systemic treatment with temsirolimus and interleukin-2 and intravitreal injections of bevacizumab. The tumor size peaked at 6.11 × 6.06 mm before the start of proton therapy, which reduced the tumor size to 5.07 × 4.39 mm.</p> <p>Conclusions</p> <p>RCC can produce metastases involving unusual sites many years after resection of the primary tumor. Proton therapy was found to be effective in treating RCC metastasis to the ciliary body in settings in which other treatment modalities failed.</p

The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis

BACKGROUND: The aim of this study was to systematically synthesise the global evidence on the prevalence of persistent symptoms in a general post COVID-19 population. METHODS: A systematic literature search was conducted using multiple electronic databases (MEDLINE and The Cochrane Library, Scopus, CINAHL, and medRxiv) until January 2022. Studies with at least 100 people with confirmed or self-reported COVID-19 symptoms at ≥28 days following infection onset were included. Patient-reported outcome measures and clinical investigations were both assessed. Results were analysed descriptively, and meta-analyses were conducted to derive prevalence estimates. This study was pre-registered (PROSPERO-ID: CRD42021238247). FINDINGS: 194 studies totalling 735,006 participants were included, with five studies conducted in those <18 years of age. Most studies were conducted in Europe (n = 106) or Asia (n = 49), and the time to follow-up ranged from ≥28 days to 387 days. 122 studies reported data on hospitalised patients, 18 on non-hospitalised, and 54 on hospitalised and non-hospitalised combined (mixed). On average, at least 45% of COVID-19 survivors, regardless of hospitalisation status, went on to experience at least one unresolved symptom (mean follow-up 126 days). Fatigue was frequently reported across hospitalised (28.4%; 95% CI 24.7%-32.5%), non-hospitalised (34.8%; 95% CI 17.6%-57.2%), and mixed (25.2%; 95% CI 17.7%-34.6%) cohorts. Amongst the hospitalised cohort, abnormal CT patterns/x-rays were frequently reported (45.3%; 95% CI 35.3%-55.7%), alongside ground glass opacification (41.1%; 95% CI 25.7%-58.5%), and impaired diffusion capacity for carbon monoxide (31.7%; 95% CI 25.8%-3.2%). INTERPRETATION: Our work shows that 45% of COVID-19 survivors, regardless of hospitalisation status, were experiencing a range of unresolved symptoms at ∼ 4 months. Current understanding is limited by heterogeneous study design, follow-up durations, and measurement methods. Definition of subtypes of Long Covid is unclear, subsequently hampering effective treatment/management strategies. FUNDING: No funding

Predictors of early death in a cohort of Ethiopian patients treated with HAART

BACKGROUND: HAART has improved the survival of HIV infected patients. However, compared to patients in high-income countries, patients in resource-poor countries have higher mortality rates. Our objective was to identify independent risk factors for death in Ethiopian patients treated with HAART. METHODS: In a district hospital in Ethiopia, we treated adult HIV infected patients with HAART based on clinical and total lymphocyte count (TLC) criteria. We measured body weight and complete blood cell count at baseline, 4 weeks later, then repeated weight every month and complete blood cell count every 12 weeks. Time to death was the main outcome variable. We used the Kaplan Meier and Cox regression survival analyses to identify prognostic markers. Also, we calculated mortality rates for the different phases of the follow-up. RESULTS: Out of 162 recruited, 152 treatment-naïve patients contributed 144.1 person-years of observation (PYO). 86 (57%) of them were men and their median age was 32 years. 24 patients died, making the overall mortality rate 16.7 per 100 PYO. The highest death rate occurred in the first month of treatment. Compared to the first month, mortality declined by 9-fold after the 18(th )week of follow-up. Being in WHO clinical stage IV and having TLC<= 750/mcL were independent predictors of death. Haemoglobin (HGB) <= 10 g/dl and TLC<= 1200/mcL at baseline were not associated with increased mortality. Body mass index (BMI) <= 18.5 kg/m2 at baseline was associated with death in univariate analysis. Weight loss was seen in about a third of patients who survived up to the fourth week, and it was associated with increased death. Decline in TLC, HGB and BMI was associated with death in univariate analysis only. CONCLUSION: The high mortality rate seen in this cohort was associated with advanced disease stage and very low TLC at presentation. Patients should be identified and treated before they progress to advanced stages. The underlying causes for early death in patients presenting at late stages should be investigated

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

Novel, Real-Time Cell Analysis for Measuring Viral Cytopathogenesis and the Efficacy of Neutralizing Antibodies to the 2009 Influenza A (H1N1) Virus

A novel electronic cell sensor array technology, the real-time cell analysis (RTCA) system, was developed to monitor cell events. Unlike the conventional methods labeling the target cells with fluorescence, luminescence, or light absorption, the RTCA system allows for label-free detection of cell processes directly without the incorporation of labels. Here, we used this new format to measure the cytopathic effect (CPE) of the 2009 influenza A (H1N1) virus and the efficacy of neutralizing antibodies in human sera to this virus. The real-time dynamic monitoring of CPE was performed on MDCK cell cultures infected with the H1N1 virus, ranging from 5.50×102 to 5.50×107 copies/mL. The resulting CPE kinetic curves were automatically recorded and were both time and viral load dependent. The CPE kinetics were also distinguishable between different H1N1 stains, as the onset of CPE induced by the A/Shanghai/37T/2009 H1N1 virus was earlier than that of the A/Shanghai/143T/2009 H1N1 virus. Furthermore, inhibition of H1N1 virus-induced CPE in the presence of human specific anti-sera was detected and quantified using the RTCA system. Antibody titers determined using this new neutralization test correlated well with those obtained independently via the standard hemagglutination inhibition test. Taken together, this new CPE assay format provided label-free and high-throughput measurement of viral growth and the effect of neutralizing antibodies, illustrating its potential in influenza vaccine studies

Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys

HIV-1-specific monoclonal antibodies (mAbs) with extraordinary potency and breadth have recently been described. In humanized mice, combinations of mAbs have been shown to suppress viremia, but the therapeutic potential of these mAbs has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific mAbs, as well as the single glycan-dependent mAb PGT121, resulted in a rapid and precipitous decline of plasma viremia to undetectable levels in rhesus monkeys chronically infected with the pathogenic virus SHIV-SF162P3. A single mAb infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa, and lymph nodes without the development of viral resistance. Moreover, following mAb administration, host Gag-specific T lymphocyte responses exhibited improved functionality. Virus rebounded in the majority of animals after a median of 56 days when serum mAb titers had declined to undetectable levels, although a subset of animals maintained long-term virologic control in the absence of further mAb infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific mAbs in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of mAb therapy for HIV-1 in humans

Optimization of the Balanced Steady State Free Precession (bSSFP) Pulse Sequence for Magnetic Resonance Imaging of the Mouse Prostate at 3T

INTRODUCTION: MRI can be used to non-invasively monitor tumour growth and response to treatment in mouse models of prostate cancer, particularly for longitudinal studies of orthotopically-implanted models. We have optimized the balanced steady-state free precession (bSSFP) pulse sequence for mouse prostate imaging. METHODS: Phase cycling, excitations, flip angle and receiver bandwidth parameters were optimized for signal to noise ratio and contrast to noise ratio of the prostate. The optimized bSSFP sequence was compared to T1- and T2-weighted spin echo sequences. RESULTS: SNR and CNR increased with flip angle. As bandwidth increased, SNR, CNR and artifacts such as chemical shift decreased. The final optimized sequence was 4 PC, 2 NEX, FA 50°, BW ±62.5 kHz and took 14-26 minutes with 200 µm isotropic resolution. The SNR efficiency of the bSSFP images was higher than for T1WSE and T2WSE. CNR was highest for T1WSE, followed closely by bSSFP, with the T2WSE having the lowest CNR. With the bSSFP images the whole body and organs of interest including renal, iliac, inguinal and popliteal lymph nodes were visible. CONCLUSION: We were able to obtain fast, high-resolution, high CNR images of the healthy mouse prostate with an optimized bSSFP sequence