Impact of the COVID-19 pandemic on osteoporotic hip fractures in Chile.

The study analyzes whether the COVID-19 pandemic affects annual hip fractures (HF) rates and weekly emergency department (ED) consultations and hospitalizations due to trauma in older people. During the COVID-19 pandemic, HF rates and ED consultation and hospitalization rates due to trauma decreased. PURPOSE: To describe the effect of the COVID-19 pandemic on annual HF rates and weekly ED consultation and hospitalization rates due to trauma in Chile in 2020, compared to 2016-2019. METHODS: A retrospective study was conducted based on data from Chile's Department of Statistics and Health Information. Annual HF admissions, weekly ED consultations and hospitalizations due to trauma were described for the years 2016-2020, grouping the years 2016-2019 to compare them with 2020. Rates were calculated per 100.000 inhabitants. RESULTS: From 2016 to 2020, a total of 35.050 patients aged ≥ 65 years were hospitalized in Chile with a diagnosis of HF, with the lowest number of admissions in 2020 (6.423). During 2020, annual HF rate was 273.6/100.000, representing a decrease of 18.5% compared to the average annual HF rate of 2016-2019 (335.7/100.000). In 2020, the weekly consultation rate due to trauma in older adults decreased by 20.8% and the weekly hospitalization rate due to trauma in older adults decreased by 18.5%. CONCLUSION: During the COVID-19 pandemic, osteoporotic HF rates decreased, along with ED consultation and hospitalization rates due to trauma in older adults. This could be a result of mobility restrictions and a significant increase in the proportion of self-reliant older adults in the Chilean population.

Decreasing hip fracture rates among older adults in Chile, 2001-2019.

Our aim was to analyze trends in hip fracture rates in people aged ≥ 65 years, from 2001 to 2019 in Chile. Age-standardized incidence rates decreased significantly in both genders over the study period. PURPOSE: To describe and analyze the characteristics and trends of osteoporotic hip fractures in Chile from 2001 to 2019, by age and sex. METHODS: We assessed hip fractures in people aged ≥ 65 years using data from the hospital discharge register of Chile's Department of Statistics and Health. The Joinpoint regression analysis software was used to perform a trend analysis. RESULTS: From 2001 to 2019, a total of 107.972 patients aged ≥ 65 years were hospitalized in Chile with a diagnosis of hip fracture (S72.0, S72.1, and S72.2). 77.4% of the patients were females, and 63.7% were adults aged ≥ 80 years. The average annual incidence rate over this period was 358.3/100.000 in the whole population (95% CI: ± 12.8), 195.2/100.000 in men (95% CI: ± 9), and 482/100.000 in women (95% CI: ± 15.5). After an adjustment for age, hip fracture rates decreased annually on average by 1.0% (p < 0.001, 95% CI: - 1.4%, - 0.7%), from 358.5/100.000 in 2001 to 331.7/100.000 in 2019. Hip fracture rates decreased annually in both men (- 1.4%, p < 0.001) and women (- 0.9%, p < 0.001). CONCLUSION: The incidence of osteoporotic hip fractures has been decreasing annually and significantly in Chile since 2001, both in men and women. This may be caused by increased levels of obesity and a lower risk of falling among older adults. We recommend further studies to assess all factors contributing to this change in hip fracture rates.

Photoactivable Ruthenium-Based Coordination Polymer Nanoparticles for Light-Induced Chemotherapy.

Green light photoactive Ru-based coordination polymer nanoparticles (CPNs), with chemical formula [[Ru(biqbpy)]1.5(bis)](PF6)3 (biqbpy = 6,6'-bis[N-(isoquinolyl)-1-amino]-2,2'-bipyridine; bis = bis(imidazol-1-yl)-hexane), were obtained through polymerization of the trans-[Ru(biqbpy)(dmso)Cl]Cl complex (Complex 1) and bis bridging ligands. The as-synthesized CPNs (50 ± 12 nm diameter) showed high colloidal and chemical stability in physiological solutions. The axial bis(imidazole) ligands coordinated to the ruthenium center were photosubstituted by water upon light irradiation in aqueous medium to generate the aqueous substituted and active ruthenium complexes. The UV-Vis spectral variations observed for the suspension upon irradiation corroborated the photoactivation of the CPNs, while High Performance Liquid Chromatography (HPLC) of irradiated particles in physiological media allowed for the first time precisely quantifying the amount of photoreleased complex from the polymeric material. In vitro studies with A431 and A549 cancer cell lines revealed an 11-fold increased uptake for the nanoparticles compared to the monomeric complex [Ru(biqbpy)(N-methylimidazole)2](PF6)2 (Complex 2). After irradiation (520 nm, 39.3 J/cm2), the CPNs yielded up to a two-fold increase in cytotoxicity compared to the same CPNs kept in the dark, indicating a selective effect by light irradiation. Meanwhile, the absence of 1O2 production from both nanostructured and monomeric prodrugs concluded that light-induced cell death is not caused by a photodynamic effect but rather by photoactivated chemotherapy.

Mechanism of Cu-Catalyzed Aryl Boronic Acid Halodeboronation Using Electrophilic Halogen: Development of a Base-Catalyzed Iododeboronation for Radiolabeling Applications.

An investigation into the mechanism of Cu-catalyzed aryl boronic acid halodeboronation using electrophilic halogen reagents is reported. Evidence is provided to show that this takes place via a boronate-driven ipso-substitution pathway and that Cu is not required for these processes to operate: general Lewis base catalysis is operational. This in turn allows the rational development of a general, simple, and effective base-catalyzed halodeboronation that is amenable to the preparation of 125I-labeled products for SPECT applications.

TGFß-Activated USP27X Deubiquitinase Regulates Cell Migration and Chemoresistance via Stabilization of Snail1.

In cancer cells, epithelial-to-mesenchymal transition (EMT) is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAF). Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box-specific E3 ligases, but its degradation is prevented in cancer cells and in activated fibroblasts. Here, we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability. Expression of USP27X in breast and pancreatic cancer cell lines and tumors positively correlated with Snail1 expression levels. Accordingly, downregulation of USP27X decreased Snail1 protein in several tumor cell lines. USP27X depletion impaired Snail1-dependent cell migration and invasion and metastasis formation and increased cellular sensitivity to cisplatin. USP27X was upregulated by TGFß during EMT and was required for TGFß-induced expression of Snail1 and other mesenchymal markers in epithelial cells and CAF. In agreement with this, depletion of USP27X prevented TGFß-induced EMT and fibroblast activation. Collectively, these results indicate that USP27X is an essential protein controlling Snail1 expression and function and may serve as a target for inhibition of Snail1-dependent tumoral invasion and chemoresistance. SIGNIFICANCE: These findings show that inhibition of USP27X destabilizes Snail1 to impair EMT and renders tumor cells sensitive to chemotherapy, thus opening new strategies for the inhibition of Snail1 expression and its protumoral actions.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/1/33/F1.large.jpg.

Diagnostic value of JC/BK virus antibody immunohistochemistry staining in urine samples from posttransplant immunosuppressed patients in relation to polyomavirus reactivation.

OBJECTIVE: To compare the diagnostic value of cytology and immunohistochemistry staining (IHS) of urine samples for polyomavirus reactivation diagnosis. STUDY DESIGN: Sixty-eight urine samples collected from 18 immunosuppressed patients were analyzed by Papanicolaou and IHS with a JC/BK virus-specific monoclonal antibody. RESULTS: Overall, polyomavirus BK (BKV) was positive in 11 of 18 patients (61.1%) (3 of whom developed hemorrhagic cystitis) and in 23 of 68 urine samples (28%). Of 23 samples, 4 (17%) were positive by 1 of the 2 techniques, only. Of 23 samples, 19 (83%) were positive by both methods. In matching urine samples from the same patient, the number of BKV-infected positive cells detected by IHS in urine slides was higher than those detected by Papanicolaou staining (71.3%). CONCLUSION: The main advantage of LHS is that it allowed confirmation of BKV infection diagnosis in urine samples. IHS detected more BKV-infected cells in samples with few positive urothelial cells, which would have gone undetected if only Papanicolaou staining had been used as the BKV screening method. Urine samples testing for BKV by both techniques will improve diagnosis in asymptomatic patients, allowing early therapeutic intervention and a better clinical outcome.

Dissection of the Kaposi's sarcoma-associated herpesvirus gene expression program by using the viral DNA replication inhibitor cidofovir.

Treatment of primary effusion lymphoma cells latently infected by Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus-8 [HHV-8]) with agents such as 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a lytic viral replication cycle, with an ordered gene expression program. Initial studies of the KSHV expression program following TPA induction using viral microarrays yielded useful information concerning the viral expression program, but precise kinetic assignments for some genes remained unclear. Classically, late herpesvirus genes require viral DNA replication for maximal expression. We used cidofovir (CDV), a nucleotide-analogue KSHV DNA polymerase inhibitor, to dissect KSHV expression into two components: genes expressed without viral DNA replication and those requiring it. The expression of known immediate-early or early genes (e.g., open reading frames [ORFs] 50, K8 bZIP, and 57) serving lytic regulatory roles was relatively unaffected by the presence of CDV, while known late capsid and tegument structural genes (e.g., ORFs 25, 26, 64, and 67) were CDV sensitive. Latency-associated transcript ORF 73 was unaffected by the presence of TPA or CDV, suggesting that it was constitutively expressed. Expression of several viral cellular gene homologs, including K2 (vIL-6), ORF 72 (vCyclin), ORF 74 (vGPCR), and K9 (vIRF-1), was unaffected by the presence of CDV, while that of others, such as K4.1 (vMIP-III), K11.1 (vIRF-2), and K10.5 (LANA2, vIRF-3), was inhibited. The results distinguish KSHV genes whose full expression required viral DNA replication from those that did not require it, providing additional insights into KSHV replication and pathogenesis strategies and helping to show which viral cell homologs are expressed at particular times during the lytic process.

Aumento de la carga viral del virus de Epstein-Barr en el momento del diagnóstico de un linfoma cerebral primario en una paciente receptora de un trasplante renal / Increase of viral load of Epstein-Barr virus at diagnosis of primary brain lymphoma in a kidney transplanted patient

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Genotypes of JC virus in East, Central and Southwest Europe.

Distinctive genotypes of JC virus have been described for the major continental landmasses. Studies on European-Americans and small cohorts in Europe showed predominantly Type 1. Types 2 and 7 are found in Asia, and Types 3 and 6 in Africa. These genotypes differ in sequence by about 1--3%. Each genotype may have several subtypes which differ from each other by about 0.5--1%. The genotypes can be defined by a distinctive pattern of nucleotides in a typing region of the VP1 gene. This genotyping approach has been confirmed by phylogenetic reconstruction using the entire genome exclusive of the rearranging regulatory region. In this first large European study, we report on the urinary excretion of JCV DNA of 350 individuals from Poland, Hungary, Germany and Spain. We included Gypsy cohorts in Hungary (Roma), Germany (Sinti), and Spain (Gitano), as well as Basques in Spain. We show that while Type 1 predominates in Europe, the proportions of Type 1A and 1B may differ from East to Southwest Europe. Type 4, closely related to the Type 1 sequence (only approximately 1% difference) was a minor genotype in Germany, Poland and Spain, but represented the majority in Basques. The Gitanos in Spain showed a variant Type 4 sequence termed 'Rom-1'. Interestingly, neither the Gitanos in Spain, nor Sinti or Roma in Germany or Hungary showed the Type 2 or Type 7 genotype that might be expected if their origins were in an Asian population.

Enfermedad de Hodgkin en pacientes con infección por el virus de la inmunodeficiencia humana. Estudio de 15 casos / Hodgkin's disease in patients infected by the human immunodeficiency virus. Study of fifteen cases

Fundamento: Aunque la enfermedad de Hodgkin (EH) no se considera como una entidad definitoria de sida, en los pacientes infectados por el VIH presenta unas características clínicas y biológicas diferenciadas. Pacientes y métodos: Estudio de las características clinicopatológicas y analíticas, de la presencia del virus de Epstein-Barr (VEB) (reacción en cadena de la polimerasa) y del pronóstico en 15 pacientes con EH e infección por el VIH diagnosticados en un solo centro durante un período de 10 años. Resultados: Trece enfermos presentaban signos B; en 10 había afección extraganglionar y 12 presentaban una EH avanzada. Los tipos histológicos más frecuentes fueron la celularidad mixta (6) y la depleción linfocítica (6). La media (DE) de linfocitos CD4 fue 0,10 (0,08) * 109/l. Se evidenció la presencia del VEB en la biopsia ganglionar en 3 de 4 pacientes analizados. Hubo respuesta completa al tratamiento en 7 de 14 pacientes (50 por ciento), la mediana de supervivencia global fue de 26 meses y la probabilidad de supervivencia libre de evento a los 2 años fue del 60 por ciento. Conclusiones: La EH en los pacientes con infección por el VIH se presenta en estadios avanzados, subtipos histológicos desfavorables, frecuente afección extraganglionar y presencia de signos B. El pronóstico es malo, lo cual se debe, sobre todo, a una baja tasa de respuesta al tratamiento (AU)

Background: In spite of not being considered as an AIDS defining illnes, Hodgkin's disease (HD) has specific clinical and biological features in HIV-infected patients. Patients and methods: Study of clinicopathologic and analytic characteristics, Epstein-Barr virus (EBV) detection (polymerase chain reaction), and prognosis in 15 patients with HD and HIV infection. Results: Thirteen patients had B symptoms, 10 extranodal involvement and 12 advanced HD. The most frequent histologic subtypes were mixed cellularity (6) and lymphocyte depletion (6). The mean (SD) of CD4 lymphocytes was 0.10 (0.08) * 109/l. The presence of EBV in lymph node biopsy was demonstrated in 3 out of 4 patients investigated. Complete remission (CR) was achieved in 7 out of 14 treated cases (50%), the median overall survival was 26 months and the 2 year event-free survival probability was 60%. Conclussions: In HIV-infected patients, HD presents in advanced stages, unfavourable histologic subtypes, frequent extranodal involvement and B symptoms. The prognosis is poor, mainly because of a low CR rate (AU)