Clinical challenges and considerations in pharmacotherapy of osteoporosis due to menopause.

INTRODUCTION: Osteoporosis is a chronic systemic skeletal disorder characterized by compromised bone strength and an increased risk of fracture, with a high prevalence worldwide. It is associated with a negative quality of life and an increased morbidity and mortality. Postmenopausal women are more prone to develop osteoporosis, and many of them will suffer at least one fragility fracture along their lifetime. AREAS COVERED: This review starts by summarizing the pathogenesis of postmenopausal osteoporosis (PMO), with focus on the estrogen deficiency-associated bone loss. It continues with the current PMO diagnostic and fracture risk prediction tools, and it finally addresses management of PMO. All the efficacy and safety profiles of the current and future osteoporosis medications are reviewed. Furthermore, strategies to optimize the long-term disease management are discussed. For this review, only publications in English language were selected. References were extracted from PubMed, Embase, and Medline. EXPERT OPINION: PMO disease management is far from being ideal. Educational and communication programs with the goal of improving disease knowledge and awareness, as well as reducing the health-care gap, should be implemented. In addition, most effective sequential prevention and treatment strategies should be initiated from the early menopause.

The assembly-defective phenotype of an FIV Gag polyprotein containing the SIV nucleocapsid zinc finger motifs is reversed by including the SIV SP2 domain in the chimeric protein.

To gain insight into the functional relationship between the nucleocapsid (NC) domains of the Gag polyproteins of feline and simian immunodeficiency viruses, FIV and SIV, respectively, we generated two FIV Gag chimeric proteins containing different SIV NC and gag sequences. A chimeric FIV Gag protein (NC1) containing the SIV two zinc fingers motifs was incapable of assembling into virus-like particles. By contrast, another Gag chimera (NC2) differing from NC1 by the replacement of the C-terminal region of the FIV NC with SIV SP2 produced particles as efficiently as wild-type FIV Gag. Of note, when the chimeric NC2 Gag polyprotein was expressed in the context of the proviral DNA in feline CrFK cells, wild-type levels of virions were produced which encapsidated 50% of genomic RNA when compared to the wild-type virus.

Analysis of the gut microbiota profile targeted to multiple hypervariable regions of 16S rRNA in a hypertensive heart failure rat model.

The gut microbiota, comprising a diverse community of microorganisms, significantly influences various aspects of health. Changes in the composition of the gut microbiota are implicated in adverse effects on host physiology, contributing to the pathogenesis of cardiovascular diseases, among others pathological conditions. Understanding the role of the gut microbiota in the context of heart failure is particularly important. In this regard, the spontaneously hypertensive heart failure (SHHF) rat is an adequate experimental model since exhibits many features in common with heart failure (HF) in humans. Recent advancements in next-generation sequencing (NGS) have greatly improved microbiome analysis. However, standardization and the adoption of best practices are essential to mitigate experimental variations across studies. This manuscript outlines a straightforward methodology for analyzing gut microbiota composition in SHHF rat fecal samples using 16S rRNA sequencing, emphasizing the relevance of gut microbiota in heart failure.

Key morphological features of human pyramidal neurons.

The basic building block of the cerebral cortex, the pyramidal cell, has been shown to be characterized by a markedly different dendritic structure among layers, cortical areas, and species. Functionally, differences in the structure of their dendrites and axons are critical in determining how neurons integrate information. However, within the human cortex, these neurons have not been quantified in detail. In the present work, we performed intracellular injections of Lucifer Yellow and 3D reconstructed over 200 pyramidal neurons, including apical and basal dendritic and local axonal arbors and dendritic spines, from human occipital primary visual area and associative temporal cortex. We found that human pyramidal neurons from temporal cortex were larger, displayed more complex apical and basal structural organization, and had more spines compared to those in primary sensory cortex. Moreover, these human neocortical neurons displayed specific shared and distinct characteristics in comparison to previously published human hippocampal pyramidal neurons. Additionally, we identified distinct morphological features in human neurons that set them apart from mouse neurons. Lastly, we observed certain consistent organizational patterns shared across species. This study emphasizes the existing diversity within pyramidal cell structures across different cortical areas and species, suggesting substantial species-specific variations in their computational properties.

Gut Microbiota Signatures with Potential Clinical Usefulness in Colorectal and Non-Small Cell Lung Cancers.

The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.

In vitro Safety Assessment of Extracts and Compounds From Plants as Sunscreen Ingredients.

This work investigated the safety of extracts obtained from plants growing in Colombia, which have previously shown UV-filter/antigenotoxic properties. The compounds in plant extracts obtained by the supercritical fluid (CO2) extraction method were identified using gas chromatography coupled to mass spectrometry (GC/MS) analysis. Cytotoxicity measured as cytotoxic concentration 50% (CC50) and genotoxicity of the plant extracts and some compounds were studied in human fibroblasts using the trypan blue exclusion assay and the Comet assay, respectively. The extracts from Pipper eriopodon and Salvia aratocensis species and the compound trans-ß-caryophyllene were clearly cytotoxic to human fibroblasts. Conversely, Achyrocline satureioides, Chromolaena pellia, and Lippia origanoides extracts were relatively less cytotoxic with CC50 values of 173, 184, and 89 µg/mL, respectively. The C. pellia and L. origanoides extracts produced some degree of DNA breaks at cytotoxic concentrations. The cytotoxicity of the studied compounds was as follows, with lower CC50 values representing the most cytotoxic compounds: resveratrol (91 µM) > pinocembrin (144 µM) > quercetin (222 µM) > titanium dioxide (704 µM). Quercetin was unique among the compounds assayed in being genotoxic to human fibroblasts. Our work indicates that phytochemicals can be cytotoxic and genotoxic, demonstrating the need to establish safe concentrations of these extracts for their potential use in cosmetics.

Adaptation of the Recreovía During COVID-19 Lockdowns: Making Physical Activity Accessible to Older Adults in Bogotá, Colombia.

The community restrictions during the coronavirus disease 2019 pandemic adversely impacted older adults' physical activity levels. This convergent mixed-method study assessed the adaptation of the Recreovía, a community-based physical activity program in Bogotá, and characterized physical activity levels among older adult participants. Our results showed how the Recreovía adapted during the pandemic to continue promoting physical activity, through indoor and outdoor strategies, including virtual physical activity sessions and safety protocols. During this time, 72%-79% of the older adults attending the adapted program were physically active. A greater proportion of park users (84.2%) and more people involved in vigorous physical activity were observed during Recreovía days. Older adults had positive experiences and perceptions of the Recreovía program related to their health and social well-being. Even though the older adults prefer being outdoors, the adapted program allowed participants to continue with their physical activity routines as much as possible during the pandemic.

Análisis cepstral de la voz normal y patológica en español colombiano mediante el uso del programa PRAAT / Cepstral analysis of normal and pathological voice in Colombian Spanish using the PRAAT program

Introducción: las medidas auditivo-perceptuales subjetivas GRABS (Grade [grado de gravedad], Roughness [aspereza], Asthenia [astenia], Breathiness [soplosidad] y Strain [tensión] y CAPE-V (Consensus Auditory-Perceptual Evaluation of Voice) han sido el estándar de oro en evaluar la voz. La prominencia del pico cepstral suavizado (CPPS) se impone como la medida acústica objetiva más robusta para evaluar la gravedad de la disfonía. Se evaluó el análisis cepstral del programa PRAAT en pacientes con voz patológica y no patológica en hablantes de español colombiano y los valores estándar para el CPPS en lenguaje conectado (CPPSc), comparado con el análisis perceptual de la voz (GRBAS). Métodos: estudio observacional y analítico de prueba diagnóstica, de corte transversal y multicéntrico, con 120 individuos. Se grabó la voz y se analizó el CPPSc con el programa PRAAT. Se aplicó la valoración auditiva-perceptual por dos evaluadores expertos para la escala GRBAS. Resultados: el promedio de edad fue 43,3 años, 64,2 % mujeres. La media del CPPSc en el grupo disfónico fue de 6,40 dB y en el grupo de normofónicos fue 8,54 dB con p=0,000. Sensibilidad de 83,6% y especificidad de 96,2 % para la voz patológica en los pacientes con valores de CPPSc menores a 7,38 dB. Hubo alta correlación del valor de CPPSc con la gravedad de la disfonía. Conclusiones: el valor del CPPSc mediante el programa PRAAT es una medida eficiente por su alta validez, bajo costo y fácil aplicación para evaluar objetivamente la disfonía y su gravedad.

Introduction: Subjective auditory-perceptual measurements, GRABS (Grade, Roughness, Asthenia, Breathiness y Strain) and CAPE-V (Consensus Auditory Perceptual Evaluation of Voice) have been the gold standard in voice evaluation. Recently, the smoothed cepstral peak prominence (CPPS) has been imposed as the acoustic measurement, objective and more robust for dysphonia severity. Objectives: The cepstral analysis of the PRAAT program was evaluated in patients with a patho-logical and non-pathological voice in Colombian Spanish speakers and the standard values for the CPPS in connected language (CPPSc), compared with the perceptual analysis of the voice (GRBAS). Methods: An observational, analytical, cross-sec-tional, multicenter diagnostic test was performed with 120 individuals. The voice was recorded and the CPPSc was analyzed with the PRAAT program. The auditory-perceptual assessment was applied by two expert evaluators for the GRBAS scale. Results: The average age was 43.3 ± 18.1 years, 64.2% were women. The mean CPPSc in the dysphonic group was 6.40 dB, while in the group of normophonic indi-viduals it was 8.54 dB, with significant differences between both groups (p=0.000). Sensitivity of 83.6% and specificity of 96.2%; for pathological voice was established in patients with CPPSc values less than 7.38 dB. A high correlation was found in the CPPSc value with the severity of dysphonia. Conclusions: The value of CPPSc through the Praat program is an efficient measure, due to its high validity, low cost and easy application to objectively evaluate dysphonia and its severity.

Short-course combination treatment for experimental chronic Chagas disease.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects millions of people in the Americas and across the world, leading to considerable morbidity and mortality. Current treatment options, benznidazole (BNZ) and nifurtimox, offer limited efficacy and often lead to adverse side effects because of long treatment durations. Better treatment options are therefore urgently required. Here, we describe a pyrrolopyrimidine series, identified through phenotypic screening, that offers an opportunity to improve on current treatments. In vitro cell-based washout assays demonstrate that compounds in the series are incapable of killing all parasites; however, combining these pyrrolopyrimidines with a subefficacious dose of BNZ can clear all parasites in vitro after 5 days. These findings were replicated in a clinically predictive in vivo model of chronic Chagas disease, where 5 days of treatment with the combination was sufficient to prevent parasite relapse. Comprehensive mechanism of action studies, supported by ligand-structure modeling, show that compounds from this pyrrolopyrimidine series inhibit the Qi active site of T. cruzi cytochrome b, part of the cytochrome bc1 complex of the electron transport chain. Knowledge of the molecular target enabled a cascade of assays to be assembled to evaluate selectivity over the human cytochrome b homolog. As a result, a highly selective and efficacious lead compound was identified. The combination of our lead compound with BNZ rapidly clears T. cruzi parasites, both in vitro and in vivo, and shows great potential to overcome key issues associated with currently available treatments.

DNDI-6174 is a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc1.

New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities that are suitable for clinical development for the treatment of Leishmania remains low. Here, we describe the discovery and preclinical development of DNDI-6174, an inhibitor of Leishmania cytochrome bc1 complex activity that originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of Leishmania species and can reduce parasite burden in animal models of infection, with the potential to approach sterile cure. No major flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 is a cytochrome bc1 complex inhibitor with acceptable development properties to enter preclinical development for visceral leishmaniasis.

[COVID-19: Association of gasometric parameters at admission with in-hospital mortality]. / COVID-19: Parámetros gasométricos al ingreso y su asociación con mortalidad hospitalaria.

INTRODUCTION: At the beginning of the SARS-CoV-2 pandemic, acute respiratory failure has been the most important cause of hospitalization in patients with COVID-19, being more severe in patients with comorbidities and risk factors. In these scenarios hypoxemia has been associated with increased mortality. Our objective was to identify parameters obtained from arterial blood gases (ABG) associated with mortality in patients with COVID-19 at hospital admission. METHODS: GSA samples obtained by breathing room air (FiO2 21%) processed in the clinical laboratory were retrospectively studied in an ABL90 flex analyzer (Radiometer). RESULTS: Acute respiratory alkalosis was the predominant acid-base disturbance. Considering those patients with respiratory failure (paO2 < 60 mmHg), "silent" hypoxemia was observed in 11/176 (6%) of studied patients. In a multivariate analysis, three gasometric parameters at admission showed a positive association with hospital mortality: paO2 (p=0.053), paO2/pO2e index (which expresses the paO2 adjusted to the paO2 expected for age) (p=0.047) and fractional saturation of hemoglobin (OxiHb%) (p=0.028). DISCUSSION: GSA generate a key contribution in understanding the pathophysiology of the COVID-19 patient: in the initial evaluation, monitoring and prognosis of this disease.

Introducción: En los inicios de la pandemia por SARSCoV-2 la insuficiencia respiratoria aguda ha sido la causa más importante de hospitalización inmediata en los pacientes con COVID-19 que acudían a los servicios de urgencias, siendo mayor la gravedad en pacientes con comorbilidades y factores de riesgo preexistentes; en estos escenarios la hipoxemia ha sido asociada a mortalidad. Nuestro objetivo fue identificar parámetros obtenidos de los gases en sangre arterial (GSA) asociados a mortalidad en pacientes con COVID-19 al ingreso hospitalario. Métodos: Se estudiaron retrospectivamente muestras de GSA obtenidos respirando aire ambiente (FiO2 21%) procesadas en el laboratorio clínico en un analizador ABL90 flex (Radiometer). Resultados: La alcalosis respiratoria aguda fue el disturbio ácido base predominante. Considerando aquellos pacientes con insuficiencia respiratoria (paO2 < 60 mmHg) se observó hipoxemia "silenciosa" en 11/176 (6%) de los pacientes estudiados. En un análisis multivariado tres parámetros gasométricos al ingreso mostraron asociación positiva a mortalidad hospitalaria: paO2 (p = 0.053), índice paO2/pO2e (que expresa la paO2 ajustada a la paO2 esperada para la edad) (p = 0.047) y saturación fraccional de hemoglobina (OxiHb%) (p = 0.028). Discusión: Los GSA generan un aporte clave en la comprensión de la fisiopatología del paciente COVID-19; en la evaluación inicial, seguimiento y pronóstico de esta enfermedad.

COVID-19: parámetros gasométricos al ingreso y su asociación con mortalidad hospitalaria / COVID-19: Association of gasometric parameters at admission with in-hospital mortality

Resumen Introducción : En los inicios de la pandemia por SARS-CoV-2 la insuficiencia respiratoria aguda ha sido la causa más importante de hospitalización inmediata en los pacientes con COVID-19 que acudían a los servicios de urgencias, siendo mayor la gravedad en pacientes con comorbilidades y factores de riesgo preexistentes; en estos escenarios la hipoxemia ha sido asociada a mortalidad. Nuestro objetivo fue identificar parámetros obtenidos de los gases en sangre arterial (GSA) asocia dos a mortalidad en pacientes con COVID-19 al ingreso hospitalario. Métodos : Se estudiaron retrospectivamente muestras de GSA obtenidos respirando aire ambiente (FiO2 21%) procesadas en el laboratorio clínico en un analizador ABL90 flex (Radiometer). Resultados : La alcalosis respiratoria aguda fue el dis turbio ácido base predominante. Considerando aquellos pacientes con insuficiencia respiratoria (paO2 < 60 mmHg) se observó hipoxemia "silenciosa" en 11/176 (6%) de los pacientes estudiados. En un análisis multivariado tres parámetros gasométricos al ingreso mostraron asocia ción positiva a mortalidad hospitalaria: paO2 (p = 0.053), índice paO2/pO2e (que expresa la paO2 ajustada a la paO2 esperada para la edad) (p = 0.047) y saturación fraccional de hemoglobina (OxiHb%) (p = 0.028). Discusión : Los GSA generan un aporte clave en la comprensión de la fisiopatología del paciente COVID-19; en la evaluación inicial, seguimiento y pronóstico de esta enfermedad.

Abstract Introduction : At the beginning of the SARS-CoV-2 pandemic, acute respiratory failure has been the most important cause of hospitalization in patients with COVID-19, being more severe in patients with comorbidi ties and risk factors. In these scenarios hypoxemia has been associated with increased mortality. Our objective was to identify parameters obtained from arterial blood gases (ABG) associated with mortality in patients with COVID-19 at hospital admission. Methods : GSA samples obtained by breathing room air (FiO2 21%) processed in the clinical laboratory were retrospectively studied in an ABL90 flex analyzer (Radi ometer). Results : Acute respiratory alkalosis was the predomi nant acid-base disturbance. Considering those patients with respiratory failure (paO2 <60 mmHg), "silent" hypox emia was observed in 11/176 (6%) of studied patients. In a multivariate analysis, three gasometric parameters at admission showed a positive association with hos pital mortality: paO2 (p=0.053), paO2/pO2e index (which expresses the paO2 adjusted to the paO2 expected for age) (p=0.047) and fractional saturation of hemoglobin (OxiHb%) (p=0.028). Discussion : GSA generate a key contribution in un derstanding the pathophysiology of the COVID-19 pa tient: in the initial evaluation, monitoring and prognosis of this disease.

Secretagogin as a marker to distinguish between different neuron types in human frontal and temporal cortex.

The principal aim of the present work was to chemically characterize the population of neurons labeled for the calcium binding protein secretagogin (SCGN) in the human frontal and temporal cortices (Brodmann's area 10 and 21, respectively). Both cortical regions are involved in many high cognitive functions that are especially well developed (or unique) in humans, but with different functional roles. The pattern of SCGN immunostaining was rather similar in BA10 and BA21, with all the labeled neurons displaying a non-pyramidal morphology (interneurons). Although SCGN cells were present throughout all layers, they were more frequently observed in layers II, III and IV, whereas in layer I they were found only occasionally. We examined the degree of colocalization of SCGN with parvalbumin (PV) and calretinin (CR), as well as with nitric oxide synthase (nNOS; the enzyme responsible for the synthesis of nitric oxide by neurons) by triple immunostaining. We looked for possible similarities or differences in the coexpression patterns of SCGN with PV, CR and nNOS between BA10 and BA21 throughout the different cortical layers (I-VI). The percentage of colocalization was estimated by counting the number of all labeled cells through columns (1,100-1,400 µm wide) across the entire thickness of the cortex (from the pial surface to the white matter) in 50 µm-thick sections. Several hundred neurons were examined in both cortical regions. We found that SCGN cells include multiple neurochemical subtypes, whose abundance varies according to the cortical area and layer. The present results further highlight the regional specialization of cortical neurons and underline the importance of performing additional experiments to characterize the subpopulation of SCGN cells in the human cerebral cortex in greater detail.

Aspectos clínicos, epidemiológicos e histopatológicos de pacientes con lesiones en la mucosa bucal / Clinical, epidemiological, histological and pathological aspects of patients with lesions in the oral mucosa i: en

Introducción: Las lesiones en la mucosa bucal constituyen un grupo heterogéneo de alteraciones, de cuyo diagnóstico temprano depende el pronóstico y el tratamiento. Objetivo: Caracterizar a pacientes con lesiones en la mucosa bucal según variables clínicas, epidemiológicas e histopatológicas. Métodos: Se realizó un estudio descriptivo, longitudinal y prospectivo de 23 pacientes con lesiones en la mucosa bucal pertenecientes a los consultorios médicos de la familia del reparto Vista Alegre, quienes fueron asistidos en la consulta de estomatología del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba desde septiembre del 2021 hasta junio del 2022. Resultados: En la serie predominaron el sexo femenino, el grupo etario de 60 y más años, la estomatitis subprótesis como lesión más frecuente (39,1 %) y los traumatismos crónicos como factores de riesgo (65,2 %); asimismo, en los pacientes remitidos al nivel secundario de atención hubo coincidencia entre los diagnósticos clínico e histopatológico (76,9 % ). Conclusiones: De la valoración clínica, epidemiológica e histopatológica de estas lesiones y de la preparación de los especialistas sobre el tema dependerá el diagnóstico definitivo.

Introduction: Lesions in the oral mucosa constitute a heterogeneous group of disorders which prognosis and treatment depend on the early diagnosis. Objective: To characterize patients with lesions in the oral mucosa according to clinical, epidemiological, histological and pathological variables. Methods: A descriptive, longitudinal and prospective study of 23 patients with lesions in the oral mucosa was carried out. They belonged to the family doctor offices from Vista Alegre neighborhood and were assisted in the Stomatology Service of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba from September, 2021 to June, 2022. Results: In the series there was a prevalence of the female sex, the 60 years and over age group, subprosthesis stomatitis as more frequent lesion (39.1%) and chronic traumatisms as risk factors (65.2%); also, in patients referred to the secondary care level there was coincidence between the clinical, histological and pathological diagnoses (76.9%). Conclusions: The final diagnosis will depend on the clinical, epidemiological, histological and pathological valuation of these lesions and on the preparation of the specialists on the topic.

Gut Microbiota and Derived Short-Chain Fatty Acids Are Linked to Evolution of Heart Failure Patients.

There is a lack of direct evidence regarding gut microbiota dysbiosis and changes in short-chain fatty acids (SCFAs) in heart failure (HF) patients. We sought to assess any association between gut microbiota composition, SCFA production, clinical parameters, and the inflammatory profile in a cohort of newly diagnosed HF patients. In this longitudinal prospective study, we enrolled eighteen newly diagnosed HF patients. At admission and after 12 months, blood samples were collected for the assessment of proinflammatory cytokines, monocyte populations, and endothelial dysfunction, and stool samples were collected for analysis of gut microbiota composition and quantification of SCFAs. Twelve months after the initial HF episode, patients demonstrated improved clinical parameters and reduced inflammatory state and endothelial dysfunction. This favorable evolution was associated with a reversal of microbiota dysbiosis, consisting of the increment of health-related bacteria, such as genus Bifidobacterium, and levels of SCFAs, mainly butyrate. Furthermore, there was a decrease in the abundance of pathogenic bacteria. In vitro, fecal samples collected after 12 months of follow-up exhibited lower inflammation than samples collected at admission. In conclusion, the favorable progression of HF patients after the initial episode was linked to the reversal of gut microbiota dysbiosis and increased SCFA production, particularly butyrate. Whether restoring butyrate levels or promoting the growth of butyrate-producing bacteria could serve as a complementary treatment for these patients deserves further studies.

Preservation of whole antibodies within ancient teeth.

Archaeological remains can preserve some proteins into deep time, offering remarkable opportunities for probing past events in human history. Recovering functional proteins from skeletal tissues could uncover a molecular memory related to the life-history of the associated remains. We demonstrate affinity purification of whole antibody molecules from medieval human teeth, dating to the 13th-15th centuries, from skeletons with different putative pathologies. Purified antibodies are intact retaining disulphide-linkages, are amenable to primary sequences analysis, and demonstrate apparent immunoreactivity against contemporary EBV antigen on western blot. Our observations highlight the potential of ancient antibodies to provide insights into the long-term association between host immune factors and ancient microbes, and more broadly retain a molecular memory related to the natural history of human health and immunity.

The Importance of the Kinematic Evaluation Methods of the Upper Limbs in Women with Breast Cancer Mastectomy: A Literature Review.

The kinematic assessment of the upper limbs in breast cancer (BC) survivors is one of the most common procedures to determine the recovery process after BC surgery. However, the methodology used is heterogeneous, finding various evaluation methods, which makes it difficult to compare results between studies. The objective of this review was to identify the technical features of the kinematic evaluation methods used in patients with mastectomy for BC. A literature review was conducted to search in electronic databases, such as PubMed, ScienceDirect, Clinical Key, Google Scholar, and Scopus. A total of 641 articles were obtained. After screening the title and the summary of the investigations, 20 manuscripts were kept for a deeper analysis. Different methodologies were found for the analysis of the kinematics of the upper limbs. Eight (40%) articles used the optoelectronic system, nine (45%) used the electromagnetic system, and three (15%) used other optoelectronic systems to assess shoulder kinematics. Each investigation studied different variables such as the type of surgery, the evaluation time, the age of the patients, the rehabilitation protocol, and so on. This makes the comparison among studies difficult, and the recovery process of the patients cannot be easily determined. In conclusion, the interpretation of the movement of the upper limbs should be easy to understand for oncologists, physiotherapists, clinicians, and researchers.

Clinical validation of 3D-printed swabs in adults and children for SARS-CoV-2 detection.

Throughout the entire coronavirus disease 19 (COVID-19) pandemic, there were disruptions in the supply chain of test materials around the world, primarily in poor- and middle-income countries. The use of 3D prints is an alternative to address swab supply shortages. In this study, the feasibility of the clinical use of 3D-printed swabs for oropharyngeal and nasopharyngeal sampling for the detection of SARS-CoV-2 infection was evaluated. For that purpose, paired samples with the 3D printed and the control swabs were taken from 42 adult patients and 10 pediatric patients, and the results obtained in the detection of SARS-CoV-2 by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) were compared. Additionally, in those cases where the result was positive for SARS-CoV-2, the viral load was calculated by means of a mathematical algorithm proposed by us. For both adults and children, satisfactory results were obtained in the detection of SARS-CoV-2 by RT-qPCR; no significant differences were found in the quantification cycle values between the 3D-printed swab samples and the control samples. Furthermore, we corroborated that the 3D-printed swabs caused less discomfort and pain at the time of sampling. In conclusion, this study shows the feasibility of routinely using 3D-printed swabs for both adults and children. In this way, it is possible to maintain local and cheaper consumption along with fewer distribution difficulties.

Cauliflower mosaic virus disease spectrum uncovers novel susceptibility factor NCED9 in Arabidopsis thaliana.

Viruses are intimately linked with their hosts and especially dependent on gene-for-gene interactions to establish successful infections. On the host side, defence mechanisms such as tolerance and resistance can occur within the same species, leading to differing virus accumulation in relation to symptomology and plant fitness. The identification of novel resistance genes against viruses and susceptibility factors is an important part of understanding viral patho-genesis and securing food production. The model plant Arabidopsis thaliana displays a wide symptom spectrum in response to RNA virus infections, and unbiased genome-wide association studies have proven a powerful tool to identify novel disease-genes. In this study we infected natural accessions of A. thaliana with the pararetrovirus cauliflower mosaic virus (CaMV) to study the phenotypic variations between accessions and their correlation with virus accumulation. Through genome-wide association mapping of viral accumulation differences, we identified several susceptibility factors for CaMV, the strongest of which was the abscisic acid synthesis gene NCED9. Further experiments confirmed the importance of abscisic acid homeostasis and its disruption for CaMV disease.

Cell consequences of loss of function of the epigenetic factor EHMT1.

EHMT1 is an epigenetic factor with histone methyltransferase activity that appears mutated in Kleefstra syndrome, a neurodevelopmental genetic disorder characterized by developmental delay, intellectual disability, and autistic-like features. Despite recent progress in the study of the function of this gene and the molecular etiology of the disease, our knowledge of how EHMT1 haploinsufficiency causes Kleefstra syndrome is still very limited. Here, we show that EHMT1 depletion in RPE1 cells leads to alterations in the morphology and distribution of different subcellular structures, such as the Golgi apparatus, the lysosomes and different cell adhesion components. EHMT1 downregulation also increases centriolar satellites detection, which may indicate a role for EHMT1 in centrosome functioning. Furthermore, the migration process is also altered in EHMT1 depleted cells, which show reduced migration capacity. We consider that the described phenotypes could open new possibilities for understanding the functional impact of EHMT1 haploinsufficiency in Kleefstra syndrome, helping to elucidate the link between epigenetic regulation and the underlying cellular mechanisms that result in this neurodevelopmental disorder. This knowledge could be relevant not only for the treatment of this syndrome, but also for other neurodevelopmental conditions that could share similar deregulated cellular pathways.