Symbiosis between nanohaloarchaeon and haloarchaeon is based on utilization of different polysaccharides.

Nano-sized archaeota, with their small genomes and limited metabolic capabilities, are known to associate with other microbes, thereby compensating for their own auxotrophies. These diminutive and yet ubiquitous organisms thrive in hypersaline habitats that they share with haloarchaea. Here, we reveal the genetic and physiological nature of a nanohaloarchaeon-haloarchaeon association, with both microbes obtained from a solar saltern and reproducibly cultivated together in vitro. The nanohaloarchaeon Candidatus Nanohalobium constans LC1Nh is an aerotolerant, sugar-fermenting anaerobe, lacking key anabolic machinery and respiratory complexes. The nanohaloarchaeon cells are found physically connected to the chitinolytic haloarchaeon Halomicrobium sp. LC1Hm. Our experiments revealed that this haloarchaeon can hydrolyze chitin outside the cell (to produce the monosaccharide N-acetylglucosamine), using this beta-glucan to obtain carbon and energy for growth. However, LC1Hm could not metabolize either glycogen or starch (both alpha-glucans) or other polysaccharides tested. Remarkably, the nanohaloarchaeon's ability to hydrolyze glycogen and starch to glucose enabled growth of Halomicrobium sp. LC1Hm in the absence of a chitin. These findings indicated that the nanohaloarchaeon-haloarchaeon association is both mutualistic and symbiotic; in this case, each microbe relies on its partner's ability to degrade different polysaccharides. This suggests, in turn, that other nano-sized archaeota may also be beneficial for their hosts. Given that availability of carbon substrates can vary both spatially and temporarily, the susceptibility of Halomicrobium to colonization by Ca Nanohalobium can be interpreted as a strategy to maximize the long-term fitness of the host.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Influence of psychiatric disorders and opioid substitution therapy on hepatitis C treatment with direct-acting antivirals in people who inject drugs. / Influencia de los trastornos psiquiátricos y la terapia de sustitución con opiáceos en el tratamiento del virus de la hepatitis c con antivirales de acción directa en usuarios de drogas por vía parenteral.

INTRODUCTION: The effectiveness of the hepatitis C virus (HCV) treatment seems to be lower in people who inject drugs (PWID). We analyze the influence of various factors as psychiatric disorders and opioid substitution therapy (OST) on the treatment with direct-acting antivirals (DAA) in this collective. PATIENTS AND METHODS: Three hundred thirty-two PWID patients were treated with DAA in 12 Spanish hospitals between 2004 and 2020. They were catalogued in recent and former consumers (if the last consumption was in the last 3 years) and several variables were included, evaluating the effectiveness of the treatment according to the viral load 12 weeks after the end of the treatment with the parameter «sustained viral response¼ (SVR12). RESULTS: 23.4% were recent consumers and 27.7% were on OST. The 41.5% had any diagnosis of psychiatric disorder. SVR12 was 84.04%, ascending to 96.21% when excluded from the analyses the patients lost to follow-up (12.7%). SVR12 was lower due to an increase in the loss to follow-up in recent consumers and other factors like OST, being in prison the last 5 years, naïve patients, generalized anxiety disorder and benzodiazepine consumption. CONCLUSIONS: The effectiveness of the HCV treatment with DAA in PWID is similar than in general population in patients whit an appropriate follow-up. It is important to maintain a closer follow-up in patients on OST, recent consumers and those with psychiatric disorders.

Plasma proteomic analysis of zebrafish following spring viremia of carp virus infection.

To better understand spring viremia of carp virus (SVCV) pathogenesis in zebrafish proteomic analysis was used to examine the plasma protein profile in SVCV-infected zebrafish. A total of 3062 proteins were identified. Of those 137, 63 and 31 proteins were enriched in blood samples harvested at 1, 2 and 5 days post SVCV infection, respectively. These altered host proteins were classified based on their biological function: 23 proteins under the response to stimulus term were identified. Interestingly, at the top of the up-regulated proteins during SVCV infection were the proteins of the vitellogenin family (Vtg) and the grass carp reovirus-induced gene (Gig) proteins. Real-time RT-PCR evaluation of samples from internal organs verified that SVCV infection induced vtg and gig2 gene expression already at day 1 post-infection. Western blot analysis revealed the presence of Vtg protein only in blood of SVCV-infected fish. This is the first proteomic study to reveal the involvement of Vtg proteins in adult fish response to viral challenge. It also highlights the role of Gig proteins as important factors in antiviral response in fish. This work provides valuable relevant insight into virus-host interaction and the identification of molecular markers of fish response to virus.

Anti-gliadin antibodies in breast milk from celiac mothers on a gluten-free diet.

PURPOSE: To analyze the presence of total IgA and anti-gliadin antibodies (AGA) in BM from CD mothers who follow a gluten-free diet (GFD) and from mothers on a normal gluten-containing diet (ND). METHODS: 218 samples of mature milk were obtained at different months of lactation (1-6) from 83 mothers (2 or more samples per mother) from Italy (Naples), The Netherlands (Leiden) and Spain (Madrid, Valencia and Reus): 42 CD mothers on GFD for more than 2 years and 41 non-CD mothers on a ND. Whey samples were analyzed for AGA-IgA by an indirect homemade ELISA and for total IgA (g/L) by a commercial ELISA kit. RESULTS: AGA-IgA was detected in BM, both in mothers on a GFD and mothers on a ND. AGA-IgA levels in both groups of mothers, CD and non-CD, show the same trend towards decreasing slightly along the months of lactation (p = 0.91). A different trend is observed for total IgA levels, decreasing markedly in CD mothers from the first month of lactation onwards but remaining stable in non-CD mothers (p = 0.048). A statistically significant association was found between the means of total IgA and AGA-IgA (p < 0.001). CONCLUSION: AGA-IgA is present in BM from mothers on a ND as well as in BM from mothers who had been on a GFD for years. This reflects the existence of a long-lasting immunological memory independent of the mother's diet. If the presence of these antibodies has any role in promoting the acquisition of gluten tolerance in the infant, our study shows that children of CD mothers would be on equal conditions as children of non-CD mothers.

Arabidopsis Responds to Alternaria alternata Volatiles by Triggering Plastid Phosphoglucose Isomerase-Independent Mechanisms.

Volatile compounds (VCs) emitted by phylogenetically diverse microorganisms (including plant pathogens and microbes that do not normally interact mutualistically with plants) promote photosynthesis, growth, and the accumulation of high levels of starch in leaves through cytokinin (CK)-regulated processes. In Arabidopsis (Arabidopsis thaliana) plants not exposed to VCs, plastidic phosphoglucose isomerase (pPGI) acts as an important determinant of photosynthesis and growth, likely as a consequence of its involvement in the synthesis of plastidic CKs in roots. Moreover, this enzyme plays an important role in connecting the Calvin-Benson cycle with the starch biosynthetic pathway in leaves. To elucidate the mechanisms involved in the responses of plants to microbial VCs and to investigate the extent of pPGI involvement, we characterized pPGI-null pgi1-2 Arabidopsis plants cultured in the presence or absence of VCs emitted by Alternaria alternata We found that volatile emissions from this fungal phytopathogen promote growth, photosynthesis, and the accumulation of plastidic CKs in pgi1-2 leaves. Notably, the mesophyll cells of pgi1-2 leaves accumulated exceptionally high levels of starch following VC exposure. Proteomic analyses revealed that VCs promote global changes in the expression of proteins involved in photosynthesis, starch metabolism, and growth that can account for the observed responses in pgi1-2 plants. The overall data show that Arabidopsis plants can respond to VCs emitted by phytopathogenic microorganisms by triggering pPGI-independent mechanisms.

Trehalose rescues glial cell dysfunction in striatal cultures from HD R6/1 mice at early postnatal development.

The pathological hallmark of Huntington disease (HD) is the intracellular aggregation of mutant huntingtin (mHTT) in striatal neurons and glia associated with the selective loss of striatal medium-sized spiny neurons. Up to the present, the role of glia in HD is poorly understood and has been classically considered secondary to neuronal disorder. Trehalose is a disaccharide known to possess many pharmacological properties, acting as an antioxidant, a chemical chaperone, and an inducer of autophagy. In this study, we analyzed at an early postnatal development stage the abnormalities observed in striatal glial cell cultures of postnatal R6/1 mice (HD glia), under baseline and stressing conditions and the protective effects of trehalose. Our data demonstrate that glial HD alterations already occur at early stages of postnatal development. After 20 postnatal days in vitro, striatal HD glia cultures showed more reactive astrocytes with increased expression of glial fibrillary acidic protein (GFAP) but with less replication capacity, less A2B5(+) glial progenitors and more microglia than wild-type (WT) cultures. HD glia had lower levels of intracellular glutathione (GSH) and was more susceptible to H2O2 and epoxomicin insults. The amount of expressed GDNF and secreted mature-BDNF by HD astrocytes were much lower than by WT astrocytes. In addition, HD glial cultures showed a deregulation of the major proteolytic systems, the ubiquitin-proteasomal system (UPS), and the autophagic pathway. This produces a defective protein quality control, indicated by the elevated levels of ubiquitination and p62 protein. Interestingly, we show that trehalose, through its capacity to induce autophagy, inhibited p62/SQSTM1 accumulation and facilitated the degradation of cytoplasmic aggregates from mHTT and α-synuclein proteins. Trehalose also reduced microglia activation and reversed the disrupted cytoskeleton of astrocytes accompanied with an increase in the replication capacity. In addition, trehalose up-regulated mature-BDNF neurotrophic factor expression and secretion, probably mediating cytoskeletal organization and helping in vesicular BDNF transport. Together, these findings indicate that glia suffers functional early changes in the disease process, changes that may contribute to HD neurodegeneration. Trehalose could be a very promising compound for treatment of HD and other diseases with abnormal protein aggregates. Furthermore our study identifies glial cells as a novel target for trehalose to induce neurotrophic and neuroprotective actions in HD.

Brain-Computer Interface application: auditory serial interface to control a two-class motor-imagery-based wheelchair.

BACKGROUND: Certain diseases affect brain areas that control the movements of the patients' body, thereby limiting their autonomy and communication capacity. Research in the field of Brain-Computer Interfaces aims to provide patients with an alternative communication channel not based on muscular activity, but on the processing of brain signals. Through these systems, subjects can control external devices such as spellers to communicate, robotic prostheses to restore limb movements, or domotic systems. The present work focus on the non-muscular control of a robotic wheelchair. METHOD: A proposal to control a wheelchair through a Brain-Computer Interface based on the discrimination of only two mental tasks is presented in this study. The wheelchair displacement is performed with discrete movements. The control signals used are sensorimotor rhythms modulated through a right-hand motor imagery task or mental idle state. The peculiarity of the control system is that it is based on a serial auditory interface that provides the user with four navigation commands. The use of two mental tasks to select commands may facilitate control and reduce error rates compared to other endogenous control systems for wheelchairs. RESULTS: Seventeen subjects initially participated in the study; nine of them completed the three sessions of the proposed protocol. After the first calibration session, seven subjects were discarded due to a low control of their electroencephalographic signals; nine out of ten subjects controlled a virtual wheelchair during the second session; these same nine subjects achieved a medium accuracy level above 0.83 on the real wheelchair control session. CONCLUSION: The results suggest that more extensive training with the proposed control system can be an effective and safe option that will allow the displacement of a wheelchair in a controlled environment for potential users suffering from some types of motor neuron diseases.

[Persistent abdominal pain caused by superior mesenteric artery and celiac trunk dissection that does not respond to conservative treatment]. / Dolor abdominal persistente por disección de arteria mesentérica superior y tronco celiaco, que no responde a tratamiento conservador.

We report the case of a 32 year old male with recurrent colic abdominal pain due to superior mesenteric artery (SMA) and celiac trunk dissection, which resolved after placing 3 stents in SMA. The patient presented atypical clinical signs and symptoms, which made the diagnosis difficult. Clinical presentation, diagnostic methods and treatment options are discussed. We started with conservative management with pain medication, anticoagulation, antihypertensive drugs and image control, but on the seventh day, after restarting oral ingestion, he presented with abdominal angina, after which we proceeded to endovascular treatment with successful results and with an uneventfully 2 year follow up.

Protein markers of Bursaphelenchus xylophilus Steiner & Buhrer, 1934 (Nickle, 1970) populations using quantitative proteomics and character compatibility.

The Pine Wood Nematode (PWN) Bursaphelenchus xylophilus is a severe forest pathogen in countries where it has been introduced and is considered a worldwide quarantine organism. In this study, protein markers for differentiating populations of this nematode were identified by studying differences among four selected Iberian and one American population. These populations were compared by quantitative proteomics (iTRAQ). From a total of 2860 proteins identified using the public database from the B. xylophilus genome project, 216 were unambiguous and significantly differentially regulated in the studied populations. Comparisons of their pairwise ratio were statistically treated and supported in order to convert them into discrete character states, suggesting that 141 proteins were not informative as population specific markers. Application of the Character Compatibility methodology on the remaining 75 proteins (belonging to families with different biological functions) excludes 27 which are incompatible among them. Considering only the compatible proteins, the method selects a subset of 30 specific unique protein markers which allowed the compared classification of the Iberian isolates. This approach makes it easier search for diagnostic tools and phylogenetic inference within species and populations of a pathogen exhibiting a high level of genetic diversity.

Improved sake metabolic profile during fermentation due to increased mitochondrial pyruvate dissimilation.

Although the decrease in pyruvate secretion by brewer's yeasts during fermentation has long been desired in the alcohol beverage industry, rather little is known about the regulation of pyruvate accumulation. In former studies, we developed a pyruvate under-secreting sake yeast by isolating a strain (TCR7) tolerant to ethyl α-transcyanocinnamate, an inhibitor of pyruvate transport into mitochondria. To obtain insights into pyruvate metabolism, in this study, we investigated the mitochondrial activity of TCR7 by oxigraphy and (13) C-metabolic flux analysis during aerobic growth. While mitochondrial pyruvate oxidation was higher, glycerol production was decreased in TCR7 compared with the reference. These results indicate that mitochondrial activity is elevated in the TCR7 strain with the consequence of decreased pyruvate accumulation. Surprisingly, mitochondrial activity is much higher in the sake yeast compared with CEN.PK 113-7D, the reference strain in metabolic engineering. When shifted from aerobic to anaerobic conditions, sake yeast retains a branched mitochondrial structure for a longer time than laboratory strains. The regulation of mitochondrial activity can become a completely novel approach to manipulate the metabolic profile during fermentation of brewer's yeasts.

[Public conversation on vaccines during the covid-19 pandemic in Argentina, 2021-2022]. / Conversación pública sobre vacunas en la pandemia de covid-19 en Argentina, 2021-2022.

In the face of declining vaccination coverage and the dissemination of health-related information, conversations in the public/mediatic digital sphere constitute a relevant study area for the field of health communication. Through a qualitative study based on the analysis of government publications, digital press, and social media, we characterize the public conversation on vaccines - in terms of topics, moments, axes, and framings in Argentina during the 2020-2021 period - marked by the debate on covid-19 vaccines. The results show that public conversation focused on covid-19 vaccination, structured in two distinct moments (vaccine production and vaccination campaign), and under moral framings grounded in vaccination as a care practice and science as an authoritative voice. Simultaneously, doubts about the safety and efficacy of vaccines shaped arguments of vaccine hesitancy, which we understand as part of extended practices associated with distrust towards institutions and reinterpretations of scientific knowledge and care.

Ante la caída de las coberturas vacunales y la circulación informativa sobre salud, las conversaciones en el entorno público/mediático digital constituyen un ámbito de estudio relevante para el campo de la comunicación en salud. A través de un estudio cualitativo, basado en el análisis de publicaciones del gobierno, la prensa digital y las redes sociales, caracterizamos la conversación pública sobre vacunas ­en términos de temas, momentos, ejes y encuadres en Argentina en el período 2020-2021­ signada por el debate sobre las vacunas covid-19. Los resultados muestran que la conversación pública se centralizó en la vacunación contra el covid-19, se estructuró en dos momentos diferenciados (producción de vacunas y campaña de vacunación) y bajo encuadres morales sustentados en la vacunación como práctica de cuidado y la ciencia como voz autorizada. En simultáneo, las dudas sobre la seguridad y eficacia de las vacunas estructuraron argumentos de reticencia vacunal, que entendemos como parte de prácticas extendidas, asociadas con las desconfianzas hacia las instituciones y reinterpretaciones del conocimiento científico y del cuidado.

Successive tendon injury in an in vivo rat overload model induces early damage and acute healing responses.

Introduction: Tendinopathy is a degenerative condition resulting from tendons experiencing abnormal levels of multi-scale damage over time, impairing their ability to repair. However, the damage markers associated with the initiation of tendinopathy are poorly understood, as the disease is largely characterized by end-stage clinical phenotypes. Thus, this study aimed to evaluate the acute tendon responses to successive fatigue bouts of tendon overload using an in vivo passive ankle dorsiflexion system. Methods: Sprague Dawley female rats underwent fatigue overloading to their Achilles tendons for 1, 2, or 3 loading bouts, with two days of rest in between each bout. Mechanical, structural, and biological assays were performed on tendon samples to evaluate the innate acute healing response to overload injuries. Results: Here, we show that fatigue overloading significantly reduces in vivo functional and mechanical properties, with reductions in hysteresis, peak stress, and loading and unloading moduli. Multi-scale structural damage on cellular, fibril, and fiber levels demonstrated accumulated micro-damage that may have induced a reparative response to successive loading bouts. The acute healing response resulted in alterations in matrix turnover and early inflammatory upregulations associated with matrix remodeling and acute responses to injuries. Discussion: This work demonstrates accumulated damage and acute changes to the tendon healing response caused by successive bouts of in vivo fatigue overloads. These results provide the avenue for future investigations of long-term evaluations of tendon overload in the context of tendinopathy.

AGC1-malate aspartate shuttle activity is critical for dopamine handling in the nigrostriatal pathway.

The mitochondrial transporter of aspartate-glutamate Aralar/AGC1 is a regulatory component of the malate-aspartate shuttle. Aralar deficiency in mouse and human causes a shutdown of brain shuttle activity and global cerebral hypomyelination. A lack of neurofilament-labeled processes is detected in the cerebral cortex, but whether different types of neurons are differentially affected by Aralar deficiency is still unknown. We have now found that Aralar-knockout (Aralar-KO) post-natal mice show hyperactivity, anxiety-like behavior, and hyperreactivity with a decrease of dopamine (DA) in terminal-rich regions. The striatum is the brain region most affected in terms of size, amino acid and monoamine content. We find a decline in vesicular monoamine transporter-2 (VMAT2) levels associated with increased DA metabolism through MAO activity (DOPAC/DA ratio) in Aralar-KO striatum. However, no decrease in DA or in the number of nigral tyrosine hydroxylase-positive cells was detected in Aralar-KO brainstem. Adult Aralar-hemizygous mice presented also increased DOPAC/DA ratio in striatum and enhanced sensitivity to amphetamine. Our results suggest that Aralar deficiency causes a fall in GSH/GSSG ratio and VMAT2 in striatum that might be related to a failure to produce mitochondrial NADH and to an increase of reactive oxygen species (ROS) in the cytosol. The results indicate that the nigrostriatal dopaminergic system is a target of Aralar deficiency.

Lipase-catalyzed synthesis of hyperbranched poly-L-lactide in an ionic liquid.

Hyperbranched poly-L-lactides have been synthesized by eROP in [C4MIM][PF6] media. The bis(hydroxymethyl)butyric acid molecule was used as the AB2 core co-monomer and immobilized lipase B from Candida antarctica as biocatalyst. The degree of branching could be controlled by the reaction conditions, with the maximum achieved being 0.21. The successful achievement of the hyperbranched structure is attributed to the high solvent power of substrates and products in the ionic liquid besides sustained lipase activity.

Unraveling the Mechanisms of Ch-SeNP Cytotoxicity against Cancer Cells: Insights from Targeted and Untargeted Metabolomics.

Although chitosan-stabilized selenium nanoparticles (Ch-SeNPs) have emerged as a promising chemical form of selenium for anticancer purposes, gathering more profound knowledge related to molecular dysfunctions contributes significantly to the promotion of their evolution as a chemotherapeutic drug. In this sense, metabolites are the end products in the flow of gene expression and, thus, the most sensitive to changes in the physiological state of a biological system. Therefore, metabolomics provides a functional readout of the biochemical activity and cell state. In the present study, we evaluated alterations in the metabolomes of HepG2 cells after the exposure to Ch-SeNPs to elucidate the biomolecular mechanisms involved in their therapeutic effect. A targeted metabolomic approach was conducted to evaluate the levels of four of the main energy-related metabolites (adenosine triphosphate (ATP); adenosine diphosphate (ADP); nicotinamide adenine dinucleotide (NAD+); and 1,4-dihydronicotinamide adenine dinucleotide (NADH)), revealing alterations as a result of exposure to Ch-SeNPs related to a shortage in the energy supply system in the cell. In addition, an untargeted metabolomic experiment was performed, which allowed for the study of alterations in the global metabolic profile as a consequence of Ch-SeNP exposure. The results indicate that the TCA cycle and glycolytic pathways were impaired, while alternative pathways such as glutaminolysis and cysteine metabolism were upregulated. Additionally, increased fructose levels suggested the induction of hypoxia-like conditions. These findings highlight the potential of Ch-SeNPs to disrupt cancer cell metabolism and provide insights into the mechanisms underlying their antitumor effects.

Assessment of pH Value and Release of Calcium Ions in Calcium Silicate Cements: An In Vitro Comparative Study.

The goal of this study was to evaluate the pH and the release of calcium from four calcium-silicate-based cements. METHODS: Four materials were tested (ProClinic MTA; Angelus MTA; ProRoot MTA; Biodentine). The palatal canal root of acrylic upper molars was filled with each cement. Afterwards, they were set in phosphate-buffered saline. Measurements were taken by atomic adsorption spectroscopy (AAS) at 3, 24, 72, 168, 336, 672, and 1008 h. The pH was measured at the same timepoints. Kruskal-Wallis tests were carried out in each period, as the Kolmogorov-Smirnov and Shapiro-Wilk tests showed no parametric results. RESULTS: Significant differences (p < 0.05) in calcium release were found at the 3-, 24-, and 72-hour evaluations. All of the analyzed groups presented a release of calcium ions up to 168 h, and the general tendency was to increase up to 672 h, with a maximum release of 25.45 mg/g in the ProRoot group. We could only observe significant differences (p < 0.05) in pH value over 168 h between the Biodentine (7.93) and Angelus MTA (7.31) groups. CONCLUSIONS: There were significant differences (p < 0.05) in calcium release. Nevertheless, no significant differences (p > 0.05) in the pH values were found at the studied timepoints, except for the values at 168 h.

Analysis of New Colposcopy Techniques in the Diagnosis and Evolution of SIL/CIN: Comparison of Colposcopy with the DSI System (COLPO-DSI Study).

Compared with conventional colposcopy, colposcopy assisted by DSI-map increases the detection of HSIL/CIN2+ and might help to identify the lesions more likely to regress. INTRODUCTION: Comparison of the performance of colposcopy assisted by dynamic spectral imaging (C-DSI) with that of conventional colposcopy (CC) in the diagnosis of cervical intraepithelial neoplasia (HSIL/CIN2 or CIN3). MATERIALS AND METHODS: A total of 1655 women were referred for colposcopy between 2012 and 2020 and included in the study. Of that total, 973 were examined by the same colposcopist with C-DSI, and 682 with CC. Comparisons between CC and C-DSI were made by using the histological diagnosis performed with a punch biopsy or loop electrosurgical excision procedure (LEEP) as the gold standard. A follow-up study was conducted until 2021 to detect progression to HSIL/CIN2 at 6, 12 and 24 months after first examination. RESULTS: C-DSI provided higher sensitivity for the diagnosis of HSIL/CIN2 or CIN 3 than CC (sensitivity of 76.8% and 86.6% vs. 54.2% and 72.2%, respectively). In negative or ASCUS/LSIL Pap smear results, C-DSI showed higher sensitivity than CC (sensitivity of 66.7% and 61.5% vs. 21.4% and 33.3%, respectively). In contrast, these differences were not observed in high-grade Pap smears. The sensitivity of C-DSI in cases with HPV16/18 infection was stronger than that of CC (73.53% vs. 56.67%). The sensitivity of C-DSI to detect the progression to HSIL/CIN2+ during follow-up was 30, 17.6 and 35.7% at 6, 12 and 24 months, respectively. CONCLUSIONS: The present study shows that C-DSI in women referred for colposcopy increases the HSIL/CIN 2-3 detection rate compared to conventional colposcopy. Nevertheless, C-DSI does not seem to be an important tool to predict the evolution of the lesions during follow-up.

Case Report: Hemophagocytic Lymphohistiocytosis Secondary to Plasmodium ovale wallikeri Infection.

We report the first known case of hemophagocytic lymphohistiocytosis (HLH) secondary to imported Plasmodium ovale wallikeri infection in a 58-year-old white woman. A delayed diagnosis of malaria and HLH was made after protracted fever and pancytopenia failed to respond adequately to antimalarial treatment, which required intravenous methylprednisolone and gamma-globulin therapy to resolve.

High-throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal-zone lymphoma.

Using high-resolution genomic microarray analysis, a distinct genomic profile was defined in 114 samples from patients with splenic marginal zone lymphoma (SMZL). Deletion or uniparental disomy of chromosome 7q were detected in 42 of 114 (37%) SMZLs but in only nine of 170 (5%) mature B-cell lymphomas (P < 0·00001). The presence of unmutated IGHV, genomic complexity, 17p13-TP53 deletion and 8q-MYC gain, but not 7q deletion, correlated with shorter overall survival of SMZL patients. Mapping studies narrowed down a commonly deleted region of 2·7 Mb in 7q32.1-q32.2 spanning a region between the SND1 and COPG2 genes. High-throughput sequencing analysis of the 7q32-deleted segment did not identify biallelic deletions/insertions or clear pathogenic gene mutations, but detected six nucleotide changes in IRF5 (n = 2), TMEM209 (n = 2), CALU (n = 1) and ZC3HC1 (n = 1) not found in healthy individuals. Comparative expression analysis found a fourfold down-regulation of IRF5 gene in lymphomas with 7q32 deletion versus non-deleted tumours (P = 0·032). Ectopic expression of IRF5 in marginal-zone lymphoma cells decreased proliferation and increased apoptosis in vitro, and impaired lymphoma development in vivo. These results show that cryptic deletions, insertions and/or point mutations inactivating genes within 7q32 are not common in SMZL, and suggest that IRF5 may be a haploinsufficient tumour suppressor in this lymphoma entity.