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Background: Arboviruses represent the most rapidly spreading mosquito-borne viruses worldwide. In Mozambique, arboviroses have been heavily neglected and for this reason they are never considered in the differential diagnosis of acute febrile illness. A recent dengue outbreak was reported in Pemba, situated in northern Mozambique in 2014, and during the outbreak more than half of dengue suspected cases had their dengue results negative, suggesting other causes of fever of unknown origin. The aim of the study was to investigate the circulation of dengue (DENV), chikungunya (CHIKV), west nile virus (WNV) and rift valley fever (RVF) in febrile and non febrile patients in Pemba, during the outbreak of dengue in 2014. Methods & Materials: A total of 398 individuals were identified, of which, 300 were non febrile and 98 were dengue suspected cases (febrile) attending the outpatient appointment visit at Pemba Provincial Hospital, between March and April 2014 were enrolled in this study. Blood samples were collected from each participant and initially tested for dengue using IgM anti-dengue commercial ELISA and by real time PCR. All dengue negative samples were then tested for chikungunya, RVFV, WNV using the PCR and indirect immunofluorescence assay (IFA) for IgG detection. Results: Of the 398 participants 37.7% (37/98) were DENV positive using PCR and all were negative for CHIKV, RVF andWNVwhen tested by PCR.Amongfebrile patients, IgG antibodies against CHIKV were detected in 27.5% (27/98) of febrile participants by IFA, 10.2% (10/98) were dual positive for IgG anti-DENV and IgG anti-CHIKV and 3.06% (3/98) were positive for IgG anti-RVF. The percentage of positive results for IgG antibodies against DENV, CHIKV, RVFV among non febrile participants were 26% (78/300), 45.3% (136/300) and 1% (3/300), respectively. No sample was positive for IgG anti- WNV antibody among non febrile patients. Conclusion: Our data provide evidence that DENV, CHIKV and RVF co-circulate in northern Mozambique, suggesting that not only DENV but CHIKV and RVFV, should be considered in the differential diagnosis of acute febrile syndrome in northern Mozambique. [ABSTRACT FROM AUTHOR]

Purpose: To characterize the risk of revision hip arthroscopy or conversion to total hip arthroplasty (THA) among patients with a history of lumbar fusion undergoing primary hip arthroscopy., Methods: We used the Statewide Planning and Research Cooperative System, an administrative database including all ambulatory and inpatient surgery encounters in New York, to identify all patients who underwent hip arthroscopy for femoroacetabular impingement between 2010 and 2020. Patients with previous lumbar fusion were identified using Current Procedural Terminology and International Classification of Diseases, Ninth and Tenth Revision, coding definitions. Patients with and without previous fusion were matched in a 1:5 ratio according to age and comorbidity burden. The number of levels fused was defined in the following fashion: (1) no fusion, (2) 1-2 levels, or (3) ≥3 levels. Patients were followed for 2 years to evaluate the rate of revision hip arthroscopy or conversion to THA. Multivariable logistic regression models were used to measure the association between number of levels fused and revision hip arthroscopy or conversion to THA., Results: Between 2010 and 2020, there were 23,277 patients who underwent primary hip arthroscopy in New York state. Of these, 348 (1.4%) had a previous lumbar fusion. After matching for age and comorbidities, the composite rate of revision hip arthroscopy or conversion to THA was greater in patients with previous lumbar fusion compared with patients without (16.5% vs 8.5%; P < .001). This risk increased with the number of levels fused (1-2 levels: 15.1%; adjusted odds ratio, 1.8; 95% confidence interval 1.3-2.6; vs ≥3 levels: 26.3%; adjusted odds ratio, 3.4; 95% confidence interval 1.7-7.0)., Conclusions: Patients with a history of lumbar fusion had significantly greater rates of revision hip arthroscopy and conversion to THA compared with patients without previous fusion. The risk of revision hip arthroscopy or conversion to THA was increased approximately 2-fold in patients with 1 to 2 levels fused and 3-fold in patients with 3 or more levels fused., Level of Evidence: Level III, prognostic retrospective matched comparative case series., Competing Interests: Disclosures All authors (A.C., K.Y., M.H.N., T.I., G.G., A.S.R.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The battle against the COVID-19 pandemic has spurred a heightened state of vigilance in global healthcare, leading to the proliferation of diverse sanitization methods. Among these approaches, germicidal lamps utilizing ultraviolet (UV) rays, particularly UV-C (wavelength ranging from 280 to 100 nm), have gained prominence for domestic use. These light-emitting diode (LED) lamps are designed to sanitize the air, objects, and surfaces. However, the prevailing concern is that these UV lamps are often introduced into the market without adequate accompanying information to ensure their safe utilization. Importantly, exposure to absorbed UV light can potentially trigger adverse biological responses, encompassing cell death and senescence. Our research encompassed a series of investigations aimed at comprehending the biological repercussions of UV-C radiation exposure from readily available domestic lamps. Our focus centered on epithelial retinal cells, keratinocytes, and fibroblasts, components of the skin and ocular targets frequently exposed to UV irradiation. Our findings underscore the potential harm associated with even brief exposure to UV, leading to irreversible and detrimental alterations in both skin cells and retinal cells of the eye. Notably, epithelial retinal cells exhibited heightened sensitivity, marked by substantial apoptosis. In contrast, keratinocytes demonstrated resilience to apoptosis even at elevated UV doses, though they were prone to senescence. Meanwhile, fibroblasts displayed a gradual amplification of both senescence and apoptosis as radiation doses escalated. In summary, despite the potential benefits offered by UV-C in deactivating pathogens like SARS-CoV-2, it remains evident that the concurrent risks posed by UV-C to human health cannot be ignored.

Although the current literature reports an acceptable rate of complications with the use of a perineal post in hip arthroscopy, they are still possible and preventable. The purpose of this study was to survey International Society for Hip Arthroscopy (ISHA) members on their use of postless distraction in hip arthroscopy. A 19-question survey was emailed to hip preservation surgeons that are members of ISHA. The questions examined surgeons' location, experience, utilization of a perineal post or postless distraction and any complications they may have encountered. In all, 145 respondents completed the survey. Regarding complications encountered when using a perineal post, the most frequent responses were temporary nerve damage (115, 80.6%), temporary genitourinary complications (39, 27%), temporary genital skin injury (35, 24%) and permanent nerve injury (12, 8%). Regarding the postless technique, of the 60 respondents who noted they have utilized postless distraction, 9 (15%) reported complications, with 7 (12%) reporting temporary nerve damage being the most common and 0 reporting cases of permanent nerve injury. These were statistically significantly less than those reported with a perineal post. Ninety-seven percent reported that after utilizing postless distraction, their patients were recovering better than or the same as when using a perineal post. This survey had excellent international participation by experienced hip arthroscopists. There were a statistically significantly decreased number of complications reported by the surgeons utilizing postless distraction. This survey highlights that postless distraction is being done successfully with lower reported complications and excellent patient recovery., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)

Several investigations on senescence and its causative role in aging have underscored the importance of developing senotherapeutics, a field focused on killing senescent cells and/or preventing their accumulation within tissues. Using polyphenols in counteracting senescence may facilitate the development of senotherapeutics given their presence in the human diet, their confirmed tolerability and absence of severe side effects, and their role in preventing senescence and inducing the death of senescent cells. Against that background, we evaluated the effect of piceatannol, a natural polyphenol, on the senescence of mesenchymal stromal cells (MSCs), which play a key role in the body's homeostasis. Among our results, piceatannol reduced the number of senescent cells both after genotoxic stress that induced acute senescence and in senescent replicative cultures. Such senotherapeutics activity, moreover, promoted the recovery of cell proliferation and the stemness properties of MSCs. Altogether, our findings demonstrate piceatannol's effectiveness in counteracting senescence by targeting its associated pathways and detecting and affecting P53-dependent and P53-independent senescence. Our study thus suggests that, given piceatannol's various mechanisms to accomplish its pleiotropic activities, it may be able to counteract any senescent phenotypes.

Senescent cells secrete several molecules, collectively named senescence-associated secretory phenotype (SASP). In the SASP of cells that became senescent following several in vitro chemical and physical stress, we identified the IGFBP-4 protein that can be considered a general stress mediator. This factor appeared to play a key role in senescence-paracrine signaling. We provided evidences showing that genotoxic injury, such as low dose irradiation, may promote an IGFBP-4 release in bloodstream both in mice irradiated with 100 mGy X-ray and in human subjects that received Computer Tomography. Increased level of circulating IGFBP-4 may be responsible of pro-aging effect. We found a significant increase of senescent cells in the lungs, heart, and kidneys of mice that were intraperitoneally injected with IGFBP-4 twice a week for two months. We then analyzed how genotoxic stressors may promote the release of IGFBP-4 and the molecular pathways associated with the induction of senescence by this protein., Competing Interests: NA, TS, GD, GG, RD, MM, GP, UG No competing interests declared, (© 2020, Alessio et al.)

Exposure to high levels of ionizing radiation (IR) (>0.5 Gy) negatively affects health, but less is known about the effects of low-dose ionizing radiation (LDIR). Recent evidence suggests that it may have profound effects on cellular functions. People are commonly exposed to LDIR over natural background levels from numerous sources, including LDIR from medical diagnosis and therapy, air travel, illegal IR waste dumpsites, and occupational exposures in the nuclear and medical sectors. Stem cells reside for long periods of time in our bodies, and this increases the possibility that they may accumulate genotoxic damage derived from extrinsic LDIR or intrinsic sources (such as DNA replication). In this review, we provide an overview of LDIR effects on the biology of stem cell compartments. The principal findings and issues reported in the scientific literature are discussed in order to present the current understanding of the LDIR exposure risk and assess whether it may impact human health. We first consider the general biological consequences of LDIR exposure. Following this, we discuss the effects of LDIR on stem cells as discovered through in vitro and in vivo studies. Stem Cells 2018;36:1146-1153., (© AlphaMed Press 2018.)

The literature on sero-epidemiological studies of flaviviral infections in the African continent is quite scarce. Much of the viral epidemiology studies have been focussing on diseases such as HIV/AIDS because of their sheer magnitude and impact on the lives of people in the various affected countries. Increasingly disease outbreaks caused by arboviruses such as the recent cases of chikungunya virus, dengue virus and yellow fever virus have prompted renewed interest in studying these viruses. International agencies from the US, several EU nations and China are starting to build collaborations to build capacity in many African countries together with established institutions to conduct these studies. The Tofo Advanced Study Week (TASW) was established to bring the best scientists from the world to the tiny seaside town of Praia do Tofo to rub shoulders with African virologists and discuss cutting-edge science and listen to the work of researchers in the field. In 2015 the 1st TASW focussed on Ebola virus. The collections of abstracts from participants at the 2nd TASW which focused on Dengue and Zika virus as well as presentations on other arboviruses are collated in this chapter.

The anti-inflammatory properties of DHA have been largely demonstrated in vitro and in vivo but research gaps remain regarding the contribution of the oxygenated metabolites. Among them, we are focusing on prostaglandin-like molecules termed Neuroprostanes (NeuroPs) which are produced through free-radical-mediated peroxidation of DHA. We hypothesized that these specific molecules which are highly reactive and produced in abundance during oxidative stress and inflammation could contribute to the anti-inflammatory properties of DHA. Human peripheral blood mononuclear cells were isolated from healthy donors by Ficoll density gradient centrifugation. Monocytes were differentiated into resting macrophages (RM) for 6 days (37°C, 5% CO2). RM were exposed to 2 different types of NeuroPs (i.e. 14-A4-NeuroP and 4-F4t-NeuroP, 10µM) or ethanol (vehicle 0.15%) during 30min. Then LPS (100ng/mL) was added for 6hours to induced inflammatory response. Both types of NeuroPs (14-A4-NeuroP and 4-F4t-NeuroP) significantly decreased the mRNA levels of IL-6 (-49% and -26% respectively) and MCP-1 (-55% and -24% respectively). Secretion of TNFα and MCP-1 was also reduced when RM were exposed to 14-A4-NeuroP (-10%, ns and -34%, p<0.05) and 4-F4t-NeuroP (-12%, p<0.01 and 25%, ns). Preliminary results regarding the expression and phosphorylation of IkBa suggest that 4-F4t-NeuroP could exert its anti-inflammatory effects through the inhibition of IkBa phosphorylation. Finally, cotransfection of luciferase reporter vector with hPPARg expression vector performed on Cos-7 cells suggests that NeuroPs probably act independently of PPARg. In conclusion, these results suggest that the anti-inflammatory properties of DHA could be mediated, at least in part, by NeuroPs which corroborates the importance of oxidative stress in cell signaling., (Copyright © 2014. Published by Elsevier Inc.)

Advances in the ability to treat various soft-tissue and osseous pathologic conditions of the hip arthroscopically have been predicated on an improved exposure of the pathology of the central, peripheral, and peritrochanteric compartments. The management of the capsule is critical and must allow for an improved exposure without compromising stability and kinematics of the hip. Described approaches have included capsulectomy, limited capsulotomy, extensile capsulotomy, capsular plication, and capsular shift. The selected approach must consider various factors, including symptomatic complaints, underlying hyperlaxity, specific mechanical pathology, and surgical expertise. Universally using a single technique without consideration of the complex mechanical and anatomic factors unique to each patient may result in incomplete treatment of the pathoanatomy or iatrogenic instability. This article reviews the anatomy of the hip capsule and provide a diagnosis-based consideration of capsular management during hip arthroscopy. The senior author's preferred techniques are also presented., (Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Vinorelbine (VRN) is one of the most representative compounds of its class: the vinca alkaloids. VRN interferes with microtubule assembly. VRN shows a better therapeutic index than the parent compound vincristine and vinblastine probably because of its higher affinity for mitotic microtubules. VNR high affinity for mitotic microtubules causes a high clinical efficacy for the treatment of non-small cell lung cancer (NSCLC) and for breast cancer (BC), together with a good tolerability at therapeutically effective doses. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. Unlike other vinca alkaloids, the catharanthine unit is the site of structural modification for VRN. The antitumor activity of VNR is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, VNR may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca²⁺-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis. The VNR is also characterized by improved hematologic tolerance and less neurotoxicity compared to parent compound. The aim of this review is 1) to explore the efficacy and tolerability of VNR in cancer therapy and 2) to examine the more recent approaches to improve the efficacy and tolerability of VNR in cancer therapy.

We previously demonstrated that quercetin, a naturally occurring flavonoid with strong antioxidant properties, was able to enhance programmed cell death in HPB-acute lymphoblastic leukemia (ALL) cell line, derived from a human tymoma, when associated with the agonistic anti-CD95 monoclonal antibody. Here, we report that HPB-ALL cells are normally resistant to CD95-mediated apoptosis, and quercetin is able to sensitize this cell line through a mechanism independent of its antioxidant properties. In fact, other compounds structurally and functionally similar to quercetin, when associated with anti-CD95 antibody did not induce any CD95-mediated apoptosis, still maintaining their antioxidant capacity. We found that quercetin effects are mediated by the activation of PKCalpha. Treatment of HPB-ALL cells with quercetin slightly decreased PKCalpha activity, but when the flavonoid was associated with anti-CD95, the kinase activity increased by 12-fold with respect to the treatment with quercetin. In addition, overexpression of PKCalpha induced programmed cell death in the absence of any additional stimulus, while a kinase-defective mutant of PKCalpha was ineffective. Our data confirm the involvement of specific PKC isoforms in CD95 signaling and suggest, for the first time, that quercetin targets this pathway increasing apoptogenic response in a cell line resistant to CD95-mediated apoptosis.

Unlike the neuroendocrine cell lines widely used to study trafficking of soluble and membrane proteins to secretory granules, the endocrine cells of the anterior pituitary are highly specialized for the production of mature secretory granules. Therefore, we investigated the trafficking of three membrane proteins in primary anterior pituitary endocrine cells. Peptidylglycine alpha-amidating monooxygenase (PAM), an integral membrane protein essential to the production of many bioactive peptides, is cleaved and enters the regulated secretory pathway even when expressed at levels 40-fold higher than endogenous levels. Myc-TMD/CD, a membrane protein lacking the lumenal, catalytic domains of PAM, is still stored in granules. Secretory granules are not the default pathway for all membrane proteins, because Tac accumulates on the surface of pituitary endocrine cells. Overexpression of PAM is accompanied by a diminution in its endoproteolytic cleavage and in its BaCl(2)-stimulated release from mature granules. Because internalized PAM/PAM-antibody complexes are returned to secretory granules, the endocytic machinery of the pituitary endocrine cells is not saturated. As in corticotrope tumor cells, expression of PAM or Myc-TMD/CD alters the organization of the actin cytoskeleton. PAM-mediated alterations in the cytoskeleton may limit maturation of PAM and storage in mature granules.

Thirteen skeletons found in the Caius Iulius Polybius house, which has been the object of intensive study since its discovery in Pompeii 250 years ago, have provided an opportunity to study either bone diagenesis by histological investigation or ancient DNA by polymerase chain reaction analysis. DNA analysis was done by amplifying both X- and Y-chromosomes amelogenin loci and Y-specific alphoid repeat locus. The von Willebrand factor (vWF) microsatellite locus on chromosome 12 was also analyzed for personal identification in two individuals showing alleles with 10/11 and 12/12 TCTA repeats, respectively. Technical problems were the scarcity of DNA content from osteocytes, DNA molecule fragmentation, microbial contamination which change bone structure, contaminating human DNA which results from mishandling, and frequent presence of Taq DNA polymerase inhibiting molecules like polyphenols and heavy metals. The results suggest that the remains contain endogenous human DNA that can be amplified and analyzed. The amplifiability of DNA corresponds to the bone preservation and dynamics of the burial conditions subsequent to the 79 A.D. eruption.

aDNA extraction and amplification procedures have been optimized for Pompeian human bone remains whose diagenesis has been determined by histological analysis. Single copy genes amplification (X and Y amelogenin loci and Y specific alphoid repeat sequences) have been performed and compared with anthropometric data on sexing.

Antisense phosphorothioate oligonucleotides, targeted against the first codon starting region of DMPK mRNA, were successfully used in K562 and HepG2 cells to decrease DMPK expression. The most effective antisense oligo, MIO1, when added to K562 cells, shows a 75% reduction of the DMPK gene expression 6 hours after addition. The same molecule, when encapsulated in liposomes, delays myotonin mRNA decrease at 24 hours after cell treatment. This considerable success with such inhibition in vitro could be utilised to generate a cell model to study myotonic dystrophy (DM) chemio-physiological alterations.