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Vegetation plays an important role in influencing the hydrodynamic behavior, ecological equilibrium and environmental characteristics of water bodies. Several previous models have been developed, to predict hydraulic conditions in vegetated rivers, but only few are actually used in practice. In This paper six analytic model derived for submerged vegetation are compared and evaluate: Klopstra et al. (1997); Stone and Shen (2002); Van velzen (2003); Baptist et al. (2007); Huthoff et al. (2007) and Yang and Choi (2010). The evaluation of the flow formulas is based on the comparison with experimental data from literature using the criteria of deviation. Most descriptors show a good performance for predicting the mean velocity for rigid vegetation. However, the flow formulas proposed by Klopstra et al. (1997) and Huthoff et al. (2007) show the best fit to experimental data. Only for experiments with law density, these models indicate an underestimation. Velocity predicted for flexible vegetation by the six models is less accurate than the prediction in the case of rigid vegetation. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic extension contracture of the knee (PECK) is common after knee injury. Initial management is conservative to improve the range of motion; if it fails, surgery may be necessary. This systematic review analyses existing literature on Judet quadricepsplasty for PECK. We will assess clinical outcomes, complications, patient satisfaction and factors that may influence its success., Methods: A search was conducted on 25 November 2023, adhering to preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed, Embase and Google Scholar were used. Search strings were ([Judet] OR [quadricepsplasty]) AND (knee) AND (stiffness) and ([Judet] OR [quadricepsplasty]) AND (knee). Inclusion criteria: English articles focused on PECK, published between 2003 and 2023, and a minimum follow-up of 24 months. Exclusion criteria: case reports, alternative techniques, knee stiffness cases not only due to trauma, a sample size of <10 patients and articles not reporting functional outcomes., Results: Among selected studies, 239 patients were considered. The average time between injury and Judet was 27 months. The population was predominantly male; the mean follow-up was 33 months. An average intraoperative knee range of motion improvement of 79.1 degrees (confidence interval 76.9; 81.3) compared to the average preoperative starting value of 30.7 degrees was observed. This improvement decreased by 13.5 degrees at the first postoperative check and by an additional 2.4 degrees at the follow-up, while maintaining an average value of bending above 90 degrees., Conclusion: Judet quadricepsplasty appears an effective technique for the management of PECK. The heterogeneity of included studies and the absence of standardized outcome measures limit the ability to draw definitive conclusions., Level of Evidence: Level III., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy. Traumatology, Knee Surgery and Arthroscopy.)

Introduction: Lead is a known toxicant that affects all tissues in the body, most notably the brains of developing children. However, there are limited data on the dynamics of lead transfer via breastmilk and its short-term and long-term consequences. Much of the available data come from areas of the world where numerous sources of lead complicate our understanding of the effects of lead exposure via breast milk., Case Presentation: We present trends in blood lead levels in a breastfeeding dyad, where the only source of lead exposure identified was prior to pregnancy, without other known ongoing lead exposures for the lactating parent or infant., Discussion and Conclusions: In this case, all lead exposure in the infant was presumed to come from in utero transmission and breastfeeding; and infant blood lead levels varied significantly with initiation and interruption of breastfeeding. This case is discussed in the context of current models for predicting transfer of lead in breastmilk and highlights pathophysiologic considerations for understanding lead transfer in the breastfeeding dyad., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: In May 2023, Romagna, Italy, faced a devastating flood resulting in 16 fatalities, forced displacement of 26,000 citizens, and significant economic losses. Due to potential water contamination, implementing public health strategies became imperative for the Local Health Authority to mitigate the health consequences, analyze the flood's impact on the local population's health, and detect early anomalies requiring timely public health interventions., Methods: Between June and July 2023, general practitioners who were part of the RespiVirNet surveillance network completed weekly structured forms. These forms collected data on individuals exposed or not to floodwaters and clinical syndromes. Rates per 1000 resident population aged > 14 were stratified by district, week of observation, and symptomatology. Missing data were addressed by imputation using second-order autoregressive modeling., Results: An incidence of 3.52 syndromes potentially related to flood water exposure per 1000 individuals (95% CI 2.82-4.35) was estimated. Ravenna, the city most affected by the flood, recorded the highest rate (6.05 per 1000, 95% CI 4.59-7.82). Incidence decreased in the weeks post-event. Anxiety, or trauma and stress symptoms, exhibited higher rates among the exposed, diminishing over weeks. The incidence for the non-exposed (12.76 per 1000, 95% CI 10.55-15.29) showed no significant territorial differences compared to the exposed ones., Conclusions: Syndromic surveillance provided timely information on the flood's health impact, revealing a higher incidence of individual syndromes among the non-exposed. This study contributes to guiding the implementation of future public health preparedness and response strategies for populations facing similar natural disasters.

Objective: The aim of this systematic review is to evaluate the effectiveness of physiotherapy treatment provided remotely via the Internet in the postoperative treatment of orthopedic patients and compare it with standard physiotherapy (face-to-face treatment or home-based treatment) in terms of motor performance, pain symptoms, and functional recovery., Methods: A systematic search of MEDLINE, Physiotherapy Evidence Database; EMBASE, SCOPUS, and CINHAL was conducted. Two independent reviewers performed study selection, data extraction, risk of bias (ROB) assessment using Cochrane ROB 2 tools, and summarize the results by Grading of Recommendations Assessment, Development, and Evaluation., Results: Eleven randomized controlled trial were selected. Pooled results showed improvement in motor performance in favor of the telerehabilitation group at 4-6 weeks (standardized mean difference -0.24, 95% confidence interval -0.45, -0.02, p  = 0.03), and these differences were close to the minimum clinically important difference for Time Up and Go test. For pain and functional recovery, the results showed differences not statistically important. The certainty of evidence ranged from moderate to very low., Conclusion: For joint replacement patients, treatment conducted via telerehabilitation appears able to provide levels of motor performance better to that achieved through home-based treatment. In contrast, conclusive evidence that telerehabilitation is comparable to standard face-to-face treatment are not available., Competing Interests: No competing financial interests exist., (© Morri Mattia et al., 2024; Published by Mary Ann Liebert, Inc.)

The Herpes Zoster (HZ) vaccination has proven both safe and effective in alleviating conditions related to HZ, leading to significant cost savings in national healthcare and social systems. In Italy, it is recommended and provided free of charge to individuals aged 65 and older. To achieve broad vaccination coverage, alongside ordinary immunization campaigns, active and catch-up campaigns were implemented. This retrospective observational study aimed to observe the vaccination coverage achieved in the Romagna Local Health Authority (LHA) during the 2023 active campaign, with a secondary goal of assessing the impact of the 2022 catch-up campaign and the 2023 active campaign compared to ordinary campaigns. As of 3 July 2023, an overall vaccine uptake of 13.5% was achieved among individuals born in 1958, with variations among the four LHA centers ranging from 10.2% to 17.7%. Catch-up and active campaigns together contributed to nearly half of the achieved coverage in Center No. 1 and a quarter in Center No. 2. Notably, individuals born in 1957, not included in the Center No. 2 catch-up campaign, reached significantly lower vaccination coverage compared to other cohorts and centers. Analyzing the use of text messages for active campaigns, it was observed that cohort groups did not show substantial differences in text-message utilization for warnings. However, having relatives who had experienced HZ-related symptoms significantly reduced the reliance on text messages as warnings. These results highlighted how catch-up and active campaigns effectively increased vaccine coverage. Nevertheless, differences in uptake among different centers within the same LHA and the limited contribution of other information sources compared to text messages suggest the necessity of designing campaigns involving all available channels and stakeholders to maximize vaccine uptake.

Corneal organoids are useful tools for disease modeling and tissue transplantation; however, they have not yet been well studied during maturation. We characterized human iPSC-derived corneal organoids at 1, 2, 3, and 4 months of development using single-cell RNA sequencing to determine the cellular heterogeneity at each stage. We found pluripotent cell clusters committed to epithelial cell lineage at 1 month; early corneal epithelial, endothelial, and stromal cell markers at 2 months; keratocytes as the largest cell population at 3 months; and a large epithelial cell population at 4 months. We compared organoid to fetal corneal development at different stages and found that 4-month organoids closely resemble the corneal cellular complexity of the fetal (16 post conception week) and adult cornea. Using RNA velocity trajectory analysis, we found that less differentiated cells appear to give rise to corneal epithelial cells during development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Many cancers originate from stem or progenitor cells hijacked by somatic mutations that drive replication, exemplified by adenomatous transformation of pulmonary alveolar epithelial type II (AT2) cells 1 . Here we demonstrate a different scenario: expression of KRAS(G12D) in differentiated AT1 cells reprograms them slowly and asynchronously back into AT2 stem cells that go on to generate indolent tumours. Like human lepidic adenocarcinoma, the tumour cells slowly spread along alveolar walls in a non-destructive manner and have low ERK activity. We find that AT1 and AT2 cells act as distinct cells of origin and manifest divergent responses to concomitant WNT activation and KRAS(G12D) induction, which accelerates AT2-derived but inhibits AT1-derived adenoma proliferation. Augmentation of ERK activity in KRAS(G12D)-induced AT1 cells increases transformation efficiency, proliferation and progression from lepidic to mixed tumour histology. Overall, we have identified a new cell of origin for lung adenocarcinoma, the AT1 cell, which recapitulates features of human lepidic cancer. In so doing, we also uncover a capacity for oncogenic KRAS to reprogram a differentiated and quiescent cell back into its parent stem cell en route to adenomatous transformation. Our work further reveals that irrespective of a given cancer's current molecular profile and driver oncogene, the cell of origin exerts a pervasive and perduring influence on its subsequent behaviour., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Oral candidiasis is an opportunistic infection that affects mainly individuals with weakened immune system. Devices used in the oral area to treat this condition include buccal films, which present advantages over both oral tablets and gels. Since candidiasis causes pain, burning, and itching, the purpose of this work was to develop buccal films loaded with both lidocaine (anesthetic) and miconazole nitrate (MN, antifungal) to treat this pathology topically. MN was loaded in microparticles based on different natural polymers, and then, these microparticles were loaded in hydroxypropyl methylcellulose-gelatin-based films containing lidocaine. All developed films showed adequate adhesiveness and thickness. DSC and XRD tests suggested that the drugs were in an amorphous state in the therapeutic systems. Microparticles based on chitosan-alginate showed the highest MN encapsulation. Among the films, those containing the mentioned microparticles presented the highest tensile strength and the lowest elongation at break, possibly due to the strong interactions between both polymers. These films allowed a fast release of lidocaine and a controlled release of MN. Due to the latter, these systems showed antifungal activity for 24 h. Therefore, the treatment of oropharyngeal candidiasis with these films could reduce the number of daily applications with respect to conventional treatments.

The human brain undergoes rapid development at mid-gestation from a pool of neural stem and progenitor cells (NSPCs) that give rise to the neurons, oligodendrocytes, and astrocytes of the mature brain. Functional study of these cell types has been hampered by a lack of precise purification methods. We describe a method for prospectively isolating ten distinct NSPC types from the developing human brain using cell-surface markers. CD24 - THY1 -/lo cells were enriched for radial glia, which robustly engrafted and differentiated into all three neural lineages in the mouse brain. THY1 hi cells marked unipotent oligodendrocyte precursors committed to an oligodendroglial fate, and CD24 + THY1 -/lo cells marked committed excitatory and inhibitory neuronal lineages. Notably, we identify and functionally characterize a transcriptomically distinct THY1 hi EGFR hi PDGFRA - bipotent glial progenitor cell (GPC), which is lineage-restricted to astrocytes and oligodendrocytes, but not to neurons. Our study provides a framework for the functional study of distinct cell types in human neurodevelopment., Competing Interests: Declaration of interests D.D.L., J.Q.H., R.S., N.U., and I.L.W. are listed as inventors on a pending patent related to this work. I.L.W. is a cofounder of Bitterroot Bio, Inc. and Pheast, Inc., neither of which are related to the current study. I.L.W. was an initial cofounder and N.U. a former employee of Stem Cells, Inc., but currently are not consultants or employees of it or its successor., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to intermittent fasting (IF) promotes rapid hepatocyte proliferation. Mechanistically, IF-induced hepatocyte proliferation is driven by the combined action of systemic FGF15 and localized WNT signaling. Hepatocyte proliferation during periods of fasting and re-feeding re-establishes a constant liver-to-body mass ratio, thus maintaining the hepatostat. This study provides the first example of dietary influence on adult hepatocyte proliferation and challenges the widely held view that liver tissue is mostly quiescent unless chemically or mechanically injured., Competing Interests: AS, YJ, BD, CL, YY, TA, PW, MM, NN, HN, ER, MF, AK, AM No competing interests declared, RN Reviewing editor, eLife, (© 2023, Sarkar et al.)

Background: Studies on SARS-CoV-2 conducted in confined settings for prolonged times allow researchers to assess how the coronavirus spreads. San Patrignano (SP), Italy, is the largest European drug rehabilitation facility., Methods: Between 15 October and 31 December 2020, all SP residents were tested for SARS-CoV-2. We analyzed the relationships between individual characteristics and being SARS-CoV-2-positive. Three selected predictive models were used to calculate the number of expected hospitalizations. For each model, we summed the estimated individual risks to obtain the expected number of hospitalizations in our sample, and we tested whether the observed and expected numbers differed., Results: Of 807 residents, 529 (65.6%) were SARS-CoV-2-positive. Of these 323 (61.1%) were symptomatic. A strong relationship was found between being positive and living connections ( p -value < 0.001). No statistically significant relationship was found with age, sex, smoking history, or comorbidities. Although 9 to 17 hospitalizations were expected, no hospitalizations were observed ( p -value < 0.001). No one died of COVID-19., Conclusions: The peculiar characteristics of SP residents or the SP environment might at least partially explain the null hospitalization rates. Despite the extreme uniqueness of our population and despite the protected environment and all precautions that were taken, the fact that the virus was able to circulate and infect a large portion of the population highlights the fundamental role of social interactions in the spread of the disease.

Elective surgeries, as joint replacement, were resumed after the first COVID-19 pandemic wave in 2020 and a phase of coexistence with the virus began. Surgery was organized in a new way that incorporated procedures aimed at reducing the risk of spreading the virus. The aim of this study is to describe the early functional results for patients undergoing hip and knee replacements at the time healthcare services were being reopened and to compare them with the same outcomes recorded in the prepandemic period. This is a controlled retrospective study. All patients consecutively admitted during 2020 and who underwent hip and knee replacement were enrolled in the study. Patient records from January to March 2020 constituted the prepandemic control group, while patient records from May to December 2020 constituted the study group. Functional recovery was described through the patient's ability to walk using antebrachial devices and to climb up and down 3 steps. The day after surgery on which these activities were first performed was also recorded. The prepandemic group consisted of 183 patients and the pandemic group of 280 patients. The mean age of patients was 66 years (±13.1), female was 44.9% and hip replacement was 66.5%. The number of patients who climbed stairs and the timing thereof was comparable for the 2 groups (68.5% vs 72.2%, respectively; P = .403). There was no significant difference in the incidence of patients able to walk with antebrachial device and incidence of pressure ulcers and major complications. Multivariate analysis confirmed that the incidence of stair climbing was not associated with the prepandemic or pandemic inclusion. During the reopening of orthopedic surgery activity, the reorganization and treatment pathway did not affect the functional outcome achieved by patients underwent joint replacement. Constant monitoring of the functional outcomes will be required so as to further increase the number of joint replacement surgeries., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The SARS-CoV-2 pandemic has differentially impacted populations across race and ethnicity. A multi-omic approach represents a powerful tool to examine risk across multi-ancestry genomes. We leverage a pandemic tracking strategy in which we sequence viral and host genomes and transcriptomes from nasopharyngeal swabs of 1049 individuals (736 SARS-CoV-2 positive and 313 SARS-CoV-2 negative) and integrate them with digital phenotypes from electronic health records from a diverse catchment area in Northern California. Genome-wide association disaggregated by admixture mapping reveals novel COVID-19-severity-associated regions containing previously reported markers of neurologic, pulmonary and viral disease susceptibility. Phylodynamic tracking of consensus viral genomes reveals no association with disease severity or inferred ancestry. Summary data from multiomic investigation reveals metagenomic and HLA associations with severe COVID-19. The wealth of data available from residual nasopharyngeal swabs in combination with clinical data abstracted automatically at scale highlights a powerful strategy for pandemic tracking, and reveals distinct epidemiologic, genetic, and biological associations for those at the highest risk., (© 2022. The Author(s).)

The development of CRISPR-based barcoding methods creates an exciting opportunity to understand cellular phylogenies. We present a compact, tunable, high-capacity Cas12a barcoding system called dual acting inverted site array (DAISY). We combined high-throughput screening and machine learning to predict and optimize the 60-bp DAISY barcode sequences. After optimization, top-performing barcodes had ∼10-fold increased capacity relative to the best random-screened designs and performed reliably across diverse cell types. DAISY barcode arrays generated ∼12 bits of entropy and ∼66,000 unique barcodes. Thus, DAISY barcodes-at a fraction of the size of Cas9 barcodes-achieved high-capacity barcoding. We coupled DAISY barcoding with single-cell RNA-seq to recover lineages and gene expression profiles from ∼47,000 human melanoma cells. A single DAISY barcode recovered up to ∼700 lineages from one parental cell. This analysis revealed heritable single-cell gene expression and potential epigenetic modulation of memory gene transcription. Overall, Cas12a DAISY barcoding is an efficient tool for investigating cell-state dynamics., Competing Interests: Declaration of interests Stanford University has filed patent applications with L.C. and N.W.H. as inventors on the basis of this work. L.C. is a member of the scientific advisory board of Arbor Biotechnologies., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

New high-throughput biochemistry techniques complement selection-based approaches and provide quantitative kinetic and thermodynamic data for thousands of protein variants in parallel. With these advances, library generation rather than data collection has become rate-limiting. Unlike pooled selection approaches, high-throughput biochemistry requires mutant libraries in which individual sequences are rationally designed, efficiently recovered, sequence-validated, and separated from one another, but current strategies are unable to produce these libraries at the needed scale and specificity at reasonable cost. Here, we present a scalable, rapid, and inexpensive approach for creating User - designed Physically Isolated Clonal-Mutant (uPIC-M) libraries that utilizes recent advances in oligo synthesis, high-throughput sample preparation, and next-generation sequencing. To demonstrate uPIC-M, we created a scanning mutant library of SpAP, a 541 amino acid alkaline phosphatase, and recovered 94% of desired mutants in a single iteration. uPIC-M uses commonly available equipment and freely downloadable custom software and can produce a 5000 mutant library at 1/3 the cost and 1/5 the time of traditional techniques., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Loss of skeletal integrity during ageing and disease is associated with an imbalance in the opposing actions of osteoblasts and osteoclasts 1 . Here we show that intrinsic ageing of skeletal stem cells (SSCs) 2 in mice alters signalling in the bone marrow niche and skews the differentiation of bone and blood lineages, leading to fragile bones that regenerate poorly. Functionally, aged SSCs have a decreased bone- and cartilage-forming potential but produce more stromal lineages that express high levels of pro-inflammatory and pro-resorptive cytokines. Single-cell RNA-sequencing studies link the functional loss to a diminished transcriptomic diversity of SSCs in aged mice, which thereby contributes to the transformation of the bone marrow niche. Exposure to a youthful circulation through heterochronic parabiosis or systemic reconstitution with young haematopoietic stem cells did not reverse the diminished osteochondrogenic activity of aged SSCs, or improve bone mass or skeletal healing parameters in aged mice. Conversely, the aged SSC lineage promoted osteoclastic activity and myeloid skewing by haematopoietic stem and progenitor cells, suggesting that the ageing of SSCs is a driver of haematopoietic ageing. Deficient bone regeneration in aged mice could only be returned to youthful levels by applying a combinatorial treatment of BMP2 and a CSF1 antagonist locally to fractures, which reactivated aged SSCs and simultaneously ablated the inflammatory, pro-osteoclastic milieu. Our findings provide mechanistic insights into the complex, multifactorial mechanisms that underlie skeletal ageing and offer prospects for rejuvenating the aged skeletal system., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Skeletal stem and progenitor cell populations are crucial for bone physiology. Characterization of these cell types remains restricted to heterogenous bulk populations with limited information on whether they are unique or overlap with previously characterized cell types. Here we show, through comprehensive functional and single-cell transcriptomic analyses, that postnatal long bones of mice contain at least two types of bone progenitors with bona fide skeletal stem cell (SSC) characteristics. An early osteochondral SSC (ocSSC) facilitates long bone growth and repair, while a second type, a perivascular SSC (pvSSC), co-emerges with long bone marrow and contributes to shape the hematopoietic stem cell niche and regenerative demand. We establish that pvSSCs, but not ocSSCs, are the origin of bone marrow adipose tissue. Lastly, we also provide insight into residual SSC heterogeneity as well as potential crosstalk between the two spatially distinct cell populations. These findings comprehensively address previously unappreciated shortcomings of SSC research., Competing Interests: TA, RS, HS, MH, MM, LK, YW, WL, MM, NN, IW, ML, CC No competing interests declared, (© 2021, Ambrosi et al.)

Abstract: The aim of the present work was to evaluate the tolerance of physiotherapy treatment implemented for patients with coronavirus disease (COVID-19) and undergoing hip surgeryCase-control study. During the period between March and May 2020, 9 patients were enrolled in the study with diagnosis of COVID-19 and hip fracture. In order to evaluate the tolerability of physiotherapy treatment a comparison group, involving 27 patients with a hip fracture but in the absence of suspicion of COVID-19 positivity, were put together. Blood saturation and heart rate, number of physiotherapy sessions, start of physiotherapy from surgery, number of healthcare providers, recovery of ambulation, execution of walking training and dyspnea measured by Borg scale were collected before and after each single physiotherapy session to describe the exercise tolerance of the patients.There are no significant differences between the two groups regarding basic characteristics. Average of Borg scale post treatment for COVID patients was 1.3 (DS = 1.3) compared to 0.6 (DS = 0.7) of non-COVID patients (P < .0005) but the breathing difficulty was light during the treatment, only 9% of COVID patients had a worsening superior of two points with Borg scale compared to 3% of non-COVID patients (P = .138). The incidence of walking recovery was 63% in the non-COVID patients group compared to 44.4% in the COVID group (P = .329).Physiotherapy treatment of patients with COVID-19 infection and undergoing surgery for hip fracture is well tolerated and should be encouraged and well monitored., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The purpose of this study was to translate the English bone tumour DUX (Bt-DUX-Eng) questionnaire for lower extremity bone tumour patients, a disease-specific quality of life (QoL) instrument, into Italian and then examine the validity of the Italian version of Bt-DUX (Bt-DUX-It). The adaptation and translation process included forward translation, back-translation, and a review of the back-translation by an expert committee. The Bt-DUX-It was validated in a sample of adolescents treated for lower extremity osteosarcoma in Italy. Assessments included the Bt-DUX, the Toronto Extremity Salvage Score (TESS), and the European Organization for Research and Treatment Core Quality of Life Questionnaire of Cancer Patients (EORTC QLQ-C30). Fifty-one patients with a median age of 20 years (range: 15-25) completed the questionnaires. The mean Bt-DUX score was 70 (range: 16.30-100). The internal consistency of the overall score and that of the Bt-DUX-It was good: Cronbach's α was 0.95. Spearman's correlation coefficient between the Bt-DUX (total and domain scores) and EORTC QLQ C30 and TESS were overall moderate to good, reaching a p -value <0.01 in all cases. The Bt-DUX-It version is a useful tool for measuring QoL in patients with bone tumour and has similar internal consistency, construct validity, and discrimination as those of the Dutch and English versions.

Older adult patients with hip fractures are 3-4 times more likely to die within one-year after surgery than general population. The study aimed to identify independent predictive factors associated with one-year mortality after hip fracture surgery. A prospective prognostic cohort study was performed. All patients aged ≥65 years, consecutively admitted in three Italian hospitals with a diagnosis of fragility hip fracture were included. Patients with periprosthetic or pathological fractures were excluded. Multivariate analysis was used to determine variables that significantly increased the risk of one-year mortality and Receiver operating characteristic (ROC) curve analysis to assess their predictive capacity on the outcome.1083 patients fulfilled the inclusion criteria and the one-year follow-up was reached in 728 patients. The 16.6% of patients died within one-year after surgery. At the multivariate analysis, advancing age (OR = 1.094, 95% CI = 1.057-1.132), higher baseline Charlson Index (OR = 1.257, 95% CI = 1.114-1.418) and Activities of Daily Living scores (OR = 1.259, 95% CI = 1.143-1.388), presence of hospital-acquired pressure ulcers (PUs) (OR = 1.579, 95% CI = 1.002-2.489) and lack recovery of ambulation (OR = 1.736, 95% CI = 1.115-2.703), were found to be independent predictive factors of one-year mortality after surgery. The area under the ROC curve of the model was 0.780 (CI95% 0.737-0.824) for one-year mortality in elderly hip fractures patients. Early ambulation and careful long-term follow-up, with attention to frailty in elderly people, should be promoted.

Body acceleration due to heartbeat-induced reaction forces can be measured as mobile phone accelerometer (m-ACC) signals. Our aim was to test the feasibility of using m-ACC to detect changes induced by stress by ultra-short heart rate variability (USV) indices (standard deviation of normal-to-normal interval-SDNN and root mean square of successive differences-RMSSD). Sixteen healthy volunteers were recruited; m-ACC was recorded while in supine position, during spontaneous breathing at rest conditions (REST) and during one minute of mental stress (MS) induced by arithmetic serial subtraction task, simultaneous with conventional electrocardiogram (ECG). Beat occurrences were extracted from both ECG and m-ACC and used to compute USV indices using 60, 30 and 10s durations, both for REST and MS. A feasibility of 93.8% in the beat-to-beat m-ACC heart rate series extraction was reached. In both ECG and m-ACC series, compared to REST, in MS the mean beat duration was reduced by 15% and RMSSD decreased by 38%. These results show that short term recordings (up to 10 s) of cardiac activity using smartphone's accelerometers are able to capture the decrease in parasympathetic tone, in agreement with the induced stimulus., Competing Interests: The authors declare no conflict of interest.

Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation., Competing Interests: DČ, MS, AT, MM, HJ, CH No competing interests declared, (© 2019, Čapek et al.)

Background: The aim of the present study was to explore whether control of balance and other factors were associated with functional recovery and walking performance in the short term in a group of patients receiving modular knee endoprosthetic reconstruction following bone tumour resection in order to provide effective suggestions for a new rehabilitation protocol., Methods: A cross-sectional study was carried out in the chemotherapy ward of an Italian hospital specialized in bone cancer. All patients consecutively treated using a modular knee endoprosthetic between January 2013 and February 2014 were included in the study. One year after surgery, various measuring instruments were used to assess the functional outcome achieved: Musculoskeletal Tumor Society rating scale, Toronto Extremity Salvage Score and specific motor tests of gait, such as gait speed and resistance. Data concerning the variables involved are as follows: bone resection, knee joint range of motion, quadriceps muscle strength and posture control. Statistical tests included correlation analysis (Pearson and Spearman correlation)., Results: Balance control was significantly correlated to all the gait tests performed. Age, duration of chemotherapy and strength of the knee extensor muscles also showed a correlation. Conversely, joint range of motion and resection percentage did not show a significant correlation., Conclusions: Rehabilitation in patients undergoing knee joint reconstruction due to cancer should include balance control exercises, which involve not only the treated limb but address the entire sensory and motor system. This extends beyond the concept of treatment aimed at improving individual functions such as joint range of motion and muscular strength., Competing Interests: The study was approved by the Ethics Committees of Istituto Ortopedico Rizzoli n.0000393, 12/01/2018). Where possible the patients were informed of the study objectives and provided written consent.Participants consented to publication of the data they provided when signing the consent form.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: The objective of this study is to describe the rehabilitative pathway of patients undergoing endoprosthetic knee replacement surgery, build reference values ​​of the functional results achieved, and identify possible prognostic factors., Methods: Prospective observational study. All patients undergoing resection and knee replacement surgery using a modular prosthesis following bone tumor resection were consecutively recruited over the last 2 years. The patients were followed for a period of 1 year, the result values ​​were collected at 3, 6 and 12 months., Results: In total, 30 patients were enrolled. The median age was 19 years with 33% of patients being female. Median values recorded for knee flexion, quadriceps strength, Toronto Extremity Salvage Score, Time Up and Go and Six Minutes Walking Test showed an improvement of 16, 25, 18, 48 and 38% from 3 to 12 months, respectively. The level and width of the resection were correlated with the mobility of the knee and the strength of the quadriceps., Conclusion: Patients undergoing knee replacement for bone tumors were able to achieve satisfactory functional outcomes from the first postoperative year. A specific assessment of outcomes can be conducted to facilitate the management of patient expectations. A very wide resection and interventions of the proximal tibia are risk factors for a poorer functional outcome.

Background: Folk prescriptions continue to be important sources of childhood lead poisoning. Nasal spray folk prescriptions for treating rhinitis has only been reported once previously as a cause of lead poisoning., Case Presentation: We identified three pediatric cases of severe lead poisoning caused by nasal spray folk medicines prescribed for treating rhinitis. The three patients had similar clinical manifestations including: severe abdominal pain, headache, pale appearance and fatigue. Liver function tests were abnormal. Blood lead levels (BLLs) of the three patients were 91 μg/dL, 91 μg/dL, and 105 μg/dL, respectively. After chelation BLLs decreased. The lead content of the three folk remedies as measured by inductively coupled plasma mass spectrometry (ICP-MS) were 14.8, 22.3, and 33.4%. All the symptoms resolved during a course of chelation therapy. There were no severe side effects of treatment., Conclusions: Nasal spray folk prescriptions for treating rhinitis may contain extremely high bio-accessible lead content and are potential sources of lead poisoning. Clinicians should be alert to this possibility especially in those children presenting with multisystem symptoms.

G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca 2+ -, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors. For the human pseudogene GPR33, we resurrect a signaling function that supports its hypothesized role as a pathogen entry site. These results demonstrate that substituting unknown chemical activators with a light switch can reveal information about protein function and provide an optically controlled protein library for exploring the physiology and therapeutic potential of understudied GPCRs.

Background: The level of functioning in people discharged from hospital after hip arthroplasty is very heterogeneous and prognostic factors are not fully understood. The aim of this study was to determine the mean level of autonomy achieved by such patients at discharge from hospital using the Iowa Level of Assistence (ILOA) scale as a measurement tool and to investigate the possible predictive factors of this autonomy., Methods: It was conducted a prospective cohort study including hip arthroplasty patients treated consecutively in 2012. Hip arthroplasty patients following fractures, revision surgery and partial replacement were excluded, as well as patients with concomitant neurologic or rheumatologic diseases or postoperative complications that did not allow to continue the rehabilitation program, and patients with a hospitalization of more than 7 days. During the last 24 h of hospital stay the physiotherapist filled in the ILOA scale and collected all data (age, gender, number of physiotherapy treatments, length of hospitalization). Statistical analysis (univariate and multivariate analysis) was performed between the variables collected and the ILOA Score., Results: The sample was composed of 167 patients. The mean score of the ILOA was 16.6 (±6.5) and gait speed had the poorest outcome 0.19 m/s - 0.43 m/s. Multivariate analysis showed that older women are most at risk of not achieving good levels of autonomy., Conclusions: In hip arthroplasty patients at discharge from hospital gait speed is severely impaired. The challenge for rehabilitation should be to recover walking ability and efficiency starting from the early post-operative period. Gender- and age-tailored rehabilitation programs should be considered by placing particular attention on elderly women.

Objective: Anxiety among community-dwelling older adults has not been studied sufficiently. The aims of this cross-sectional population-based study were to estimate the point prevalence of clinically relevant anxiety symptoms and to describe their socio-demographic and clinical features, with particular focus on the association with somatic illnesses., Methods: Three-hundred-sixty-six non-demented older adults (mean age 83.7±6.2, range 74-99 years) from the Faenza Project (Northern Italy) were assessed using the Cambridge Mental Disorders of the Elderly Examination-Revised (CAMDEX-R) and the Geriatric Anxiety Inventory short form (GAI-sf). Multi-adjusted regression analyses were used to estimate Odds Ratio (OR) and 95% Confidence Intervals (95% CI)., Results: Clinically relevant anxiety symptoms occurred in one out of five participants (point prevalence 21.0%) and were significantly associated with depression (OR 5.6 per rank; 95% CI: 3.1-10.1), physical morbidity (OR 3.5 per illness; 95% CI: 1.0-11.9) and female gender (OR 2.8; 95% CI: 1.4-5.5). Further, there were significant associations with a consumption of alcohol exceeding 1 alcoholic unit/day., Conclusions: Anxiety symptoms are very common in older subjects, especially when medically ill. Depression and alcohol consumption often co-occur with late-life anxiety symptoms, thus requiring special attention in daily clinical practice.

The phosphoinositide 5-kinase (PIKfyve) is a critical enzyme for the synthesis of PtdIns(3,5)P2, that has been implicated in various trafficking events associated with the endocytic pathway. We have now directly compared the effects of siRNA-mediated knockdown of PIKfyve in HeLa cells with a specific pharmacological inhibitor of enzyme activity. Both approaches induce changes in the distribution of CI-M6PR and trans-Golgi network (TGN)-46 proteins, which cycles between endosomes and TGN, leading to their accumulation in dispersed punctae, whilst the TGN marker golgin-245 retains a perinuclear disposition. Trafficking of CD8-CI-M6PR (retromer-dependent) and CD8-Furin (retromer-independent) chimeras from the cell surface to the TGN is delayed following drug administration, as is the transport of the Shiga toxin B-subunit. siRNA knockdown of PIKfyve produced no defect in epidermal growth factor receptor (EGFR) degradation, unless combined with knockdown of its activator molecule Vac14, suggesting that a low threshold of PtdIns(3,5)P2 is necessary and sufficient for this pathway. Accordingly pharmacological inhibition of PIKfyve results in a profound block to the lysosomal degradation of activated epidermal growth factor (EGF) and Met receptors. Immunofluorescence revealed EGF receptors to be trapped in the interior of a swollen endosomal compartment. In cells starved of amino acids, PIKfyve inhibition leads to the accumulation of the lipidated form of GFP-LC3, a marker of autophagosomal structures, which can be visualized as fluorescent punctae. We suggest that PIKfyve inhibition may render the late endosome/lysosome compartment refractory to fusion with both autophagosomes and with EGFR-containing multivesicular bodies.