RETRACTED ARTICLE: Painful os intermetatarseum in athletes: a literature review of this condition is presented

Painful os intermetatarseum is a very rare condition. Gruber et al. first described os intermetatarseum in 1877. This condition is usually asymptomatic. One should consider painful os intermetatarseum as being a possible cause of dorsal foot pain in athletes. Surgical excision of the os intermetatarseum should be considered for those patients failing conservative treatment. Here, a literature review of this condition is presented

Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer

Funding Information: Acknowledgments: Rui M. Bernardino is supported by Fundacao para a Ciencia e a Tecnologia (2022.13386.BD). Publisher Copyright: © 2023 European Association of UrologyBackground: The presence of cribriform morphology and intraductal carcinoma (IDC) in prostate biopsies and radical prostatectomy specimens is an adverse prognostic feature that can be used to guide treatment decisions. Objective: To assess how accurately biopsies can detect cribriform morphology and IDC cancer by examining matched biopsy and prostatectomy samples. Design, setting, and participants: Patients who underwent radical prostatectomy at The Princess Margaret Cancer Centre between January 2015 and December 2022 and had cribriform morphology and/or IDC in the surgical specimen were included in the study. Outcome measurements and statistical analysis: We used detection sensitivity to evaluate the level of agreement between biopsy and prostatectomy samples regarding the presence of cribriform morphology and IDC. Results and limitations: Of the 287 men who underwent radical prostatectomy, 241 (84%) had cribriform morphology and 161 (56%) had IDC on final pathology. The sensitivity of prostate biopsy, using radical prostatectomy as the reference, was 42.4% (95% confidence interval [CI] 36–49%) for detection of cribriform morphology and 44.1% (95% CI 36–52%) for detection of IDC. The sensitivity of prostate biopsy for detection of either IDC or cribriform morphology was 52.5% (95% CI 47–58%). Among patients who underwent multiparametric magnetic resonance imaging–guided biopsies, the sensitivity was 54% (95% CI 39–68%) for detection of cribriform morphology and 37% (95% CI 19–58%) for detection of IDC. Conclusions: Biopsy has low sensitivity for detecting cribriform morphology and IDC. These limitations should be incorporated into clinical decision-making. Biomarkers for better detection of these histological patterns are needed. Patient summary: Prostate biopsy is not an accurate method for detecting two specific types of prostate cancer cells, called cribriform pattern and intraductal prostate cancer, which are associated with unfavorable prognosis.proofepub_ahead_of_prin

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

Cardiopulmonary resuscitation in low-resource settings: a statement by the International Liaison Committee on Resuscitation, supported by the AFEM, EUSEM, IFEM, and IFRC.

Most recommendations on cardiopulmonary resuscitation were developed from the perspective of high-resource settings with the aim of applying them in these settings. These so-called international guidelines are often not applicable in low-resource settings. Organisations including the International Liaison Committee on Resuscitation (ILCOR) have not sufficiently addressed this problem. We formed a collaborative group of experts from various settings including low-income, middle-income, and high-income countries, and conducted a prospective, multiphase consensus process to formulate this ILCOR Task Force statement. We highlight the discrepancy between current cardiopulmonary resuscitation guidelines and their applicability in low-resource settings. Successful existing initiatives such as the Helping Babies Breathe programme and the WHO Emergency Care Systems Framework are acknowledged. The concept of the chainmail of survival as an adaptive approach towards a framework of resuscitation, the potential enablers of and barriers to this framework, and gaps in the knowledge are discussed, focusing on low-resource settings. Action points are proposed, which might be expanded into future recommendations and suggestions, addressing a large diversity of addressees from caregivers to stakeholders. This statement serves as a stepping-stone to developing a truly global approach to guide resuscitation care and science, including in health-care systems worldwide

Are p.I148T, p.R74W and p.D1270N cystic fibrosis causing mutations ?

BACKGROUND: To contribute further to the classification of three CFTR amino acid changes (p.I148T, p.R74W and p.D1270N) either as CF or CBAVD-causing mutations or as neutral variations. METHODS: The CFTR genes from individuals who carried at least one of these changes were extensively scanned by a well established DGGE assay followed by direct sequencing and familial segregation analysis of mutations and polymorphisms. RESULTS: Four CF patients (out of 1238) originally identified as carrying the p.I148T mutation in trans with a CF mutation had a second mutation (c.3199del6 or a novel mutation c.3395insA) on the p.I148T allele. We demonstrate here that the deletion c.3199del6 can also be associated with CF without p.I148T. Three CBAVD patients originally identified with the complex allele p.R74W-p.D1270N were also carrying p.V201M on this allele, by contrast with non CF or asymptomatic individuals including the mother of a CF child, who were carrying p.R74W-p.D1270N alone. CONCLUSION: These findings question p.I148T or p.R74W-p.D1270N as causing by themselves CF or CBAVD and emphazises the necessity to perform a complete scanning of CFTR genes and to assign the parental alleles when novel missense mutations are identified

Total elbow arthroplasty: a prospective clinical outcome study of Discovery Elbow System with a 4-year mean follow-up

BACKGROUND: Total elbow arthroplasty (TEA) is increasingly used for the treatment of advanced elbow conditions to reduce pain and improve function. However, TEA is still associated with a higher complication rate than total hip and knee arthroplasty despite advances in the design and surgical techniques. This prospective clinical study reports the outcome of the Discovery Elbow System (Biomet, Warsaw IN, USA), which has been in clinical use in the United Kingdom since 2003. METHODS: The study included a total of 100 Discovery Elbows (April 2003 to January 2010) with a minimum 2-year follow-up, including 75 primary and 25 revisions (60% women and 40% men; mean age, 62 years). Outcome was assessed by means of the Liverpool Elbow Score, pain experience, patient satisfaction, range of motion, and radiographic imaging. RESULTS: The mean follow-up period was 48.5 months (range, 24-108 months). The Liverpool Elbow Score improved from 3.79 to 6.36 (P < .001). The percentage of pain-free patients was substantially increased from 7% preoperatively to 64% at the final follow-up. The patient satisfaction rate was over 90%. The flexion-extension arc and pronation-supination arc increased from 72° to 93° and from 86° to 111°, respectively (P < .001). Major postoperative complications included deep infection (2%), progressive aseptic loosening requiring revision (primary, 5%; revision 12%), persistent ulnar neuropathy (3%), and periprosthetic fracture (primary, 6.8%; revision, 8%). CONCLUSION: The Discovery Elbow System resulted in improved function, reduced pain, and high patient satisfaction. Long-term results are required to assess the survivorship of this syste

Pathways to Injury in Chronic Pancreatitis: Decoding the Role of the High-Risk SPINK1 N34S Haplotype Using Meta-Analysis

Background: The complex interactions between recurrent trypsin-mediated pancreatic injury, alcohol-associated pancreatic injury and SPINK1 polymorphisms in chronic pancreatitis (CP) are undefined. We hypothesize that CP occurs as a result of multiple pathological mechanisms (pathways) that are initiated by different metabolic or environmental factors (etiologies) and may be influenced differentially by downstream genetic risk factors. We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reports of SPINK1 N34S frequency using meta-analysis. Methods and Findings: The Pubmed and the Embase databases were reviewed. We studied 24 reports of SPINK1 N34S in CP (2,421 cases, 4,857 controls) using reported etiological factors as surrogates for pathways and multiple meta-analyses to determine the differential effects of SPINK1 N34S between alcoholic and non-alcoholic etiologies. Using estimates of between-study heterogeneity, we sub-classified our 24 studies into four specific clusters. We found that SPINK1 N34S is strongly associated with CP overall (OR 11.00; 95% CI: 7.59-15.93), but the effect of SPINK1 N34S in alcoholic CP (OR 4.98, 95% CI: 3.16-7.85) was significantly smaller than in idiopathic CP (OR 14.97, 95% C.I. = 9.09-24.67) or tropical CP (OR 19.15, 95% C.I. = 8.83-41.56). Studies analyzing familial CP showed very high heterogeneity suggestive of a complex etiology with an I2 = 80.95%. Conclusion: The small effect of SPINK1 N34S in alcoholic subjects suggests that CP is driven through a different pathway that is largely trypsin-independent. The results also suggest that large effect sizes of SPINK1 N34S in small candidate gene studies in CP may be related to a mixture of multiple etiologic pathways leading to the same clinical endpoint. © 2008 Aoun MD et al

Surfactant secretion in LRRK2 knock-out rats : changes in lamellar body morphology and rate of exocytosis

Leucine-rich repeat kinase 2 (LRRK2) is known to play a role in the pathogenesis of various diseases including Parkinson disease, morbus Crohn, leprosy and cancer. LRRK2 is suggested to be involved in a number of cell biological processes such as vesicular trafficking, transcription, autophagy and lysosomal pathways. Recent histological studies of lungs of LRRK2 knock-out (LRRK2 -/-) mice revealed significantly enlarged lamellar bodies (LBs) in alveolar type II (ATII) epithelial cells. LBs are large, lysosome-related storage organelles for pulmonary surfactant, which is released into the alveolar lumen upon LB exocytosis. In this study we used high-resolution, subcellular live-cell imaging assays to investigate whether similar morphological changes can be observed in primary ATII cells from LRRK2 -/- rats and whether such changes result in altered LB exocytosis. Similarly to the report in mice, ATII cells from LRRK2 -/- rats contained significantly enlarged LBs resulting in a >50% increase in LB volume. Stimulation of ATII cells with ATP elicited LB exocytosis in a significantly increased proportion of cells from LRRK2 -/- animals. LRRK2 -/- cells also displayed increased intracellular Ca2+ release upon ATP treatment and significant triggering of LB exocytosis. These findings are in line with the strong Ca2+-dependence of LB fusion activity and suggest that LRRK2 -/- affects exocytic response in ATII cells via modulating intracellular Ca2+ signaling. Post-fusion regulation of surfactant secretion was unaltered. Actin coating of fused vesicles and subsequent vesicle compression to promote surfactant expulsion were comparable in cells from LRRK2 -/- and wt animals. Surprisingly, surfactant (phospholipid) release from LRRK2 -/- cells was reduced following stimulation of LB exocytosis possibly due to impaired LB maturation and surfactant loading of LBs. In summary our results suggest that LRRK2 -/- affects LB size, modulates intracellular Ca2+ signaling and promotes LB exocytosis upon stimulation of ATII cells with ATP