Application of the galactomannan gel from Cassia grandis seeds for biomedical purposes: Study of the incorporation of collagenases and their release profile.

The galactomannan-based gel from Cassia grandis seeds was used to incorporate Penicillium sp. UCP 1286 and commercial collagenases. Experiments were carried out according to a 23-full factorial design to identify the most significant parameters for the incorporation process. The pH of the incorporation solution (pHi), stirring time (t), and initial protein concentration in the crude extract (PCi) were selected as the three independent variables, and the efficiency of collagenase incorporation (E) and collagenolytic activity (CA) after 360 min as the responses. pHi and PCi showed positive statistically significant effects on E, while CA was positively influenced by pHi and t, but negatively by PCi. The fungi collagenase was released from the gel following a pseudo-Fickian behavior. Additionally, no <76 % of collagenase was efficiently incorporated into the gel retaining a high CA (32.5-69.8 U/mL). The obtained results for the commercial collagenase (E = 93.88 %, CA = 65.8 U/mL, and n = 0.10) demonstrated a pseudo-Fickian behavior similar to the fungi-collagenase. The results confirm the biotechnological potential of the gel as an efficient matrix for the incorporation of catalytic compounds; additionally, the incorporation of collagenases was achieved by retaining the proteases CA and releasing them in a controlled manner.

Genomic epidemiology and antifungal-resistant characterization of Candida auris, Colombia, 2016-2021.

Since 2016, in Colombia, ongoing transmission of Candida auris has been reported in multiple cities. Here, we provide an updated description of C. auris genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from C. auris cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from C. auris cases were described in a phylogenetic analysis. All C. auris cases were clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogotá, Colombia, which grouped with isolates from Venezuela. The largest cluster (N = 166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from César; of these, 85% (N = 22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% (N = 38) were resistant to amphotericin B. Mutations in the ERG11 and TAC1B genes were identified in fluconazole-resistant isolates. This work describes molecular mechanisms associated with C. auris antifungal resistance in Colombia. Overall, C. auris cases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades of C. auris into Colombia. IMPORTANCE: Candida auris is an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission of C. auris and provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this provide information about the evolving C. auris burden that could help guide public health strategies to control C. auris spread.

Ambiguities in Preventing Infections in Nursing Homes: Care Workers Experiences and Implications for Future Policies.

Preventing infections in nursing homes is highly challenging, given the ambiguous nature of nursing homes as care institutions and places to live. Yet, little is known about how care workers experience preventing infections in this context. Understanding the ambiguities experienced by care workers in nursing homes when enacting infection prevention is crucial to preparing for future health crises. This study investigates and identifies the ambiguities care workers faced and experienced when preventing infections during the COVID-19 pandemic. Interviews and observations were combined to capture narratives and behaviors related to infection prevention and care work. By using thematic analysis, three types of ambiguity were identified: (a) an Ambiguous sense of purpose, (b) Environmental ambiguity, and (c) Information ambiguity. The findings provide a nuanced understanding of the ambiguities care workers face and experience in nursing homes when preventing infections and indicate that such ambiguities impact their behaviors and attitudes. From this study, it is possible to conclude that policymakers must consider nursing homes' ambiguous characteristics in infection prevention programs.

Preventing infections in nursing homes entails performing behaviors related to hygiene in the ambiguous context of being both a home and a care institution.Care workers experience ambiguity of purpose, environmental ambiguity and information ambiguity when preventing infections in nursing homes.Infection prevention policies need to consider nursing homes' ambiguous characteristics to respond to health crises in the future.Particular attention must be paid to the ambiguities experienced by care workers.

Indirect impact of PCV10 children vaccination on the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in adults over 50 in Colombia, 2005-2019: Observational analysis.

INTRODUCTION: The introduction of pneumococcal conjugate vaccine (PCV) into childhood vaccination programmes has reduced the prevalence of vaccine serotypes (VTs) that cause invasive pneumococcal disease (IPD) in children. In the elderly population, an impact has also been seen through indirect protection (herd effect). The aim of this study was to estimate the changes in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates recovered from adult IPD and to evaluate the indirect effect of immunization with PCV10 based on laboratory records by analyzing the period from 2005 to 2019 for six years before and eight years after the universal PCV10 administration to Colombian children. METHODS: A total of 2204 S. pneumoniae isolates from adults (≥50 years) with IPD were analyzed. The analysis examined the percentage changes in proportions (prevalence) and percentage variations in population rates (annual reported rates - ARR) of VTs between the pre-PCV10 (2005-2009) and post-PCV10 (2015-2019) periods. RESULTS: The findings were (1) evidence of a significant percentage decrease of pneumococcal VT10 causing IPD in adults (50% pre-PCV10 and 16% post-PCV10); (2) significant increase of serotype 19A (from 1.6% to 14.8%) and less important increase of serotype 3 (from 10.5% to 14.5%) and non-vaccine serotypes (NVT) (from 21.4% to 38.4%) non-significant; and (3) meningitis and non-meningitis multidrug resistant isolates associated with serotype 19A. An improvement in the surveillance system is associated with the immunization of children, as noted by the increased ARRs across the analysis period. CONCLUSIONS: Our results show the indirect impact of PCV10 vaccination in children on the VT10 distribution and antimicrobial resistance of S. pneumoniae causing IPD in Colombian adults over 50 when comparing the pre-PCV10 (2005-2009) and post-PCV10 (2015-2019) periods.

A One Health approach based on genomics for enhancing the Salmonella enterica surveillance in Colombia.

Objectives: This study aimed to provide evidence of the domestic benefits of introducing an integrative genomic analysis from the One Health approach in the national surveillance of Salmonella enterica between 1997-2017 in Colombia. Methods: Data on Salmonella from clinical laboratory-based surveillance between 1997-2017 and from a national cross-sectional study at chicken retail stores in Colombia were compared using a phenotypic, molecular, and genomic approaches. Additional analysis by serovar using single nucleotide polymorphism was developed to increase the resolution of the relatedness between the interfaces. Results: Locally, the diversity and pathogenic factors of the prevalent S. enterica serovars associated with foodborne disease in Colombia were described using laboratory, pulse field gel electrophoresis, and whole genome sequencing data. For example, the resolution of pulse field gel electrophoresis allowed the description of two main foodborne clusters of Salmonella Enteritidis isolates, which were expanded to eight foodborne clades using whole genome sequencing. Likewise, virulence factors and antimicrobial resistance determinants, and mobile genetic elements that converged in the foodborne clades should be considered a public health concern in Colombia. All results by serovar were compiled in an interactive easy to share report. Conclusion: Whole genome sequencing is a technology that provides a precise assessment of emerging foodborne risks such as the Salmonella foodborne clades, but it requires an integrative and continued collaboration between the stakeholders across the One Health sectors to promote appropriated actions and policies in public health.

Effects of IL-34 and anti-IL-34 neutralizing mAb on alveolar bone loss in a ligature-induced model of periodontitis.

Macrophage colony-stimulating factor (M-CSF) and interleukin-34 (IL-34) are ligands for the colony-stimulating factor-1  receptor (CSF-1r) expressed on the surface of monocyte/macrophage lineage cells. The importance of coordinated signaling between M-CSF/receptor activator of the nuclear factor kappa-Β ligand (RANKL) in physiological and pathological bone remodeling and alveolar bone loss in response to oral bacterial colonization is well established. However, our knowledge about the IL-34/RANKL signaling in periodontal bone loss remains limited. Recently published cohort studies have demonstrated that the expression patterns of IL-34 are dramatically elevated in gingival crevicular fluid collected from patients with periodontitis. Therefore, the present study aims to evaluate the effects of IL-34 on osteoclastogenesis in vitro and in experimental ligature-mediated model of periodontitis using male mice. Our initial in vitro study demonstrated increased RANKL-induced osteoclastogenesis of IL-34-primed osteoclast precursors (OCPs) compared to M-CSF-primed OCPs. Using an experimental model of ligature-mediated periodontitis, we further demonstrated elevated expression of IL-34 in periodontal lesions. In contrast, M-CSF levels were dramatically reduced in these periodontal lesions. Furthermore, local injections of mouse recombinant IL-34 protein significantly elevated cathepsin K activity, increased the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and promoted alveolar bone loss in periodontitis lesions. In contrast, anti-IL-34 neutralizing monoclonal antibody significantly reduced the level of alveolar bone loss and the number of TRAP-positive osteoclasts in periodontitis lesions. No beneficial effects of locally injected anti-M-CSF neutralizing antibody were observed in periodontal lesions. This study illustrates the role of IL-34 in promoting alveolar bone loss in periodontal lesions and proposes the potential of anti-IL34 monoclonal antibody (mAb)-based therapeutic regimens to suppress alveolar bone loss in periodontitis lesions.

Fatal acute undifferentiated febrile illness among clinically suspected leptospirosis cases in Colombia, 2016-2019.

BACKGROUND: Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile patients may result in medical complications or preventable deaths. Common causes of acute undifferentiated febrile illness in Colombia include leptospirosis, rickettsioses, dengue fever, malaria, chikungunya, and Zika virus infection. In this study, we described the acute undifferentiated febrile illness in postmortem patients reported as suspected cases of leptospirosis through the national leptospirosis surveillance in Colombia, 2016-2019. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyze human fresh and formalin-fixed tissue samples from fatal suspected leptospirosis cases reported by the Public Health Laboratories in Colombia. Leptospirosis confirmation was made by immunohistochemistry, real-time polymerase chain reaction (PCR) in the tissue samples. In some cases, the serum sample was used for confirmation by Microagglutination test (MAT). Simultaneously, tissue samples were tested by PCR for the most common viral (dengue, Zika, and chikungunya), bacterial (Brucella spp., and Rickettsia spp.), and parasitic (malaria). Fresh tissue samples from 92 fatal suspected leptospirosis cases were reported to the National Reference Laboratory from 22/32 departments in Colombia. We confirmed leptospirosis in 27% (25/92) of cases. Other pathogens identified by real-time PCR were Brucella spp. (10.9%), Rickettsia spp. (14.1%), and dengue (2.2%). Dengue (6.9%), hepatitis (3.5%), and Yellow Fever cases (2.2%) were detected by the pathology. All patients were negative for chikungunya and Plasmodium spp. Most cases were classified as undifferentiated febrile illnesses (45.7%; 42/92). CONCLUSIONS/SIGNIFICANCE: This study underscores the importance of early and accurate recognition of leptospirosis to prevent mortalities. Moreover, it draws attention to the existence of other febrile syndromes in Colombia, including rickettsiosis and brucellosis, that currently lack sufficient human surveillance and regular reporting. Expanding laboratory surveillance to include viruses such as Hantavirus, Mayaro virus, Oropouche virus, and West Nile virus is crucial.

Characterization of extended spectrum ß-lactamases in Colombian clinical isolates of non-typhoidal Salmonella enterica between 1997 and 2022 / Caracterización de ß-lactamasas de espectro extendido en aislamientos clínicos colombianos de Salmonella enterica no tifoidea de 1997 a 2022.

Introduction. Salmonella spp. is a zoonotic pathogen transmitted to humans through contaminated water or food. The presence of extended-spectrum ß-lactamases is a growing public health problem because these enzymes are resistant to third and fourth generation cephalosporins. Objective. To characterize extended-spectrum ß-lactamases in Salmonella spp. isolates received by the acute diarrheal disease/foodborne disease surveillance program of the Grupo de Microbiología of the Instituto Nacional de Salud. Materials and methods. A total of 444 Salmonella spp. isolates, resistant to at least one of the cephalosporins, were obtained between January 1997 and June 2022. The extendedspectrum ß-lactamases phenotype was identified by the double disk test. DNA extraction was carried out by the boiling method, and the blaCTX-M, blaSHV, and blaTEM genes were amplified by PCR. Results. All the isolates were positive for the extended-spectrum ß-lactamases test. The genes identified were: blaCTX-M + blaTEM (n=200), blaCTX-M (n=177), blaSHV (n=16), blaSHV + blaCTX-M (n=6), blaTEM (n=13) and blaSHV + blaCTX-M + blaTEM (n=3). Twenty-six isolates were negative for the evaluated genes. Positive extended-spectrum ß-lactamases isolates were identified in Bogotá and 21 departments: Chocó, Magdalena, Meta, Bolívar, Casanare, Cesar, Córdoba, Quindío, Atlántico, Tolima, Cauca, Cundinamarca, Huila, Boyacá, Caldas, Norte de Santander, Risaralda, Antioquia, Nariño, Santander y Valle del Cauca. Conclusion. Resistance to third generation cephalosporins in Salmonella spp. isolates was mainly caused by blaCTX-M. Isolates were resistant to ampicillin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole (44 %; 197/444). The most frequent extended-spectrum ß-lactamases-expressing serotypes were Salmonella Typhimurium and Salmonella Infantis.

Introducción. Salmonella spp. es un agente patógeno zoonótico transmitido al humano por el agua o los alimentos contaminados. La presencia de ß-lactamasas de espectro extendido es un creciente problema para la salud pública debido a que estas enzimas confieren resistencia contra las cefalosporinas de tercera y cuarta generación. Objetivo. Caracterizar las ß-lactamasas de espectro extendido en aislamientos de Salmonella spp. recibidos por el programa de vigilancia de enfermedad diarreica aguda o enfermedad transmitida por alimentos del Grupo de Microbiología del Instituto Nacional de Salud. Materiales y métodos. Entre enero de 1997 y junio de 2022, se recibieron 444 aislamientos de Salmonella spp. resistentes, por lo menos, a una de las cefalosporinas de tercera generación. El fenotipo de las ß-lactamasas de espectro extendido se identificó con la prueba de doble disco. El ADN se extrajo por ebullición y mediante PCR se amplificaron los genes blaCTX-M, blaSHV y blaTEM. Resultados. Todos los aislamientos fueron positivos para la prueba de ß-lactamasas de espectro extendido. Los resultados de la amplificación por PCR fueron: blaCTX-M + blaTEM (n=200), blaCTX-M (n=177), blaSHV (n=16), blaSHV + blaCTX-M (n=6), blaTEM (n=13) y blaSHV + blaCTX-M + blaTEM (n=3). Del total, 26 aislamientos fueron negativos para los genes evaluados. Los aislamientos positivos para ß-lactamasas de espectro extendido se identificaron en Bogotá y en 21 departamentos: Chocó, Magdalena, Meta, Bolívar, Casanare, Cesar, Córdoba, Quindío, Atlántico, Tolima, Cauca, Cundinamarca, Huila, Boyacá, Caldas, Norte de Santander, Risaralda, Antioquia, Nariño, Santander y Valle del Cauca. Conclusión. La resistencia a las cefalosporinas de tercera generación en aislamientos de Salmonella spp. fue generada principalmente por blaCTX-M. El 44 % (197/444) de los aislamientos presentó resistencia a ampicilina, tetraciclina, cloranfenicol y trimetoprimsulfametoxazol Los serotipos portadores de ß-lactamasas de espectro extendido más frecuentes fueron S. Typhimurium y S. Infantis.

Bacteremia by non-O1/non-O139 Vibrio cholerae: Case description and literature review. / Bacteriemia por Vibrio cholerae no-O1/no-O139: descripción de un caso y revisión de la literatura

Bacteremia by non-O1/non-O139 Vibrio cholerae is a rare entity associated with high mortality rates. We report a case of non-O1/non-O139 V. cholerae bacteremia confirmed by polymerase chain reaction and agglutination tests. The clinicoepidemiological characteristics and therapeutic options for this infection are also described.

La bacteriemia por V. cholerae no-O1/no-O139 es una entidad poco frecuente que se asocia con altas tasas de mortalidad. Reportamos un caso de bacteriemia por V. cholerae no-O1/no-O139 confirmado por reacción en cadena de la polimerasa (PCR) y test de aglutinación. Se describen además las características clínico-epidemiológicas y opciones terapéuticas para esta infección.

IL-34 exacerbates pathogenic features of Alzheimer's disease and calvaria osteolysis in triple transgenic (3x-Tg) female mice.

Hallmark features of Alzheimer's disease (AD) include elevated accumulation of aggregated Aß40 and Aß42 peptides, hyperphosphorylated Tau (p-Tau), and neuroinflammation. Emerging evidence indicated that interleukin-34 (IL-34) contributes to AD and inflammatory osteolysis via the colony-stimulating factor-1 receptor (CSF-1r). In addition, CSF-1r is also activated by macrophage colony-stimulating factor-1 (M-CSF). While the role of M-CSF in bone physiology and pathology is well addressed, it remains controversial whether IL-34-mediated signaling promotes osteolysis, neurodegeneration, and neuroinflammation in relation to AD. In this study, we injected 3x-Tg mice with mouse recombinant IL-34 protein over the calvaria bone every other day for 42 days. Then, behavioral changes, brain pathology, and calvaria osteolysis were evaluated using various behavioral maze and histological assays. We demonstrated that IL-34 administration dramatically elevated AD-like anxiety and memory loss, pathogenic amyloidogenesis, p-Tau, and RAGE expression in female 3x-Tg mice. Furthermore, IL-34 delivery promoted calvaria inflammatory osteolysis compared to the control group. In addition, we also compared the effects of IL-34 and M-CSF on macrophages, microglia, and RANKL-mediated osteoclastogenesis in relation to AD pathology in vitro. We observed that IL-34-exposed SIM-A9 microglia and 3x-Tg bone marrow-derived macrophages released significantly elevated amounts of pro-inflammatory cytokines, TNF-α, IL-1ß, and IL-6, compared to M-CSF treatment in vitro. Furthermore, IL-34, but not M-CSF, elevated RANKL-primed osteoclastogenesis in the presence of Aß40 and Aß42 peptides in bone marrow derived macrophages isolated from female 3x-Tg mice. Collectively, our data indicated that IL-34 elevates AD-like features, including behavioral changes and neuroinflammation, as well as osteoclastogenesis in female 3x-Tg mice.

An Alzheimer's disease risk variant in TTC3 modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons.

A missense variant in the tetratricopeptide repeat domain 3 (TTC3) gene (rs377155188, p.S1038C, NM_003316.4:c 0.3113C>G) was found to segregate with disease in a multigenerational family with late-onset Alzheimer's disease. This variant was introduced into induced pluripotent stem cells (iPSCs) derived from a cognitively intact individual using CRISPR genome editing, and the resulting isogenic pair of iPSC lines was differentiated into cortical neurons. Transcriptome analysis showed an enrichment for genes involved in axon guidance, regulation of actin cytoskeleton, and GABAergic synapse. Functional analysis showed that the TTC3 p.S1038C iPSC-derived neuronal progenitor cells had altered 3-dimensional morphology and increased migration, while the corresponding neurons had longer neurites, increased branch points, and altered expression levels of synaptic proteins. Pharmacological treatment with small molecules that target the actin cytoskeleton could revert many of these cellular phenotypes, suggesting a central role for actin in mediating the cellular phenotypes associated with the TTC3 p.S1038C variant.

Bacteremia by non-O1/non-O139 Vibrio cholerae: Case description and literature review / Bacteriemia por Vibrio cholerae no-O1/no-O139: descripción de un caso y revisión de la literatura

Bacteremia by non-O1/non-O139 Vibrio cholerae is a rare entity associated with high mortality rates. We report a case of non-O1/non-O139 V. cholerae bacteremia confirmed by polymerase chain reaction and agglutination tests. The clinicoepidemiological characteristics and therapeutic options for this infection are also described.

La bacteriemia por Vibrio cholerae no-O1/no-O139 es una entidad poco frecuente que se asocia con altas tasas de mortalidad. Se reporta un caso de bacteriemia por V. cholerae no-O1/no-O139 confirmado por reacción en cadena de la polimerasa y test de aglutinación. Se describen las características clinicoepidemiológicas y las opciones terapéuticas para esta infección.

Caracterización de ß-lactamasas de espectro extendido en aislamientos clínicos colombianos de Salmonella enterica no tifoidea de 1997 a 2022 / Characterization of extended spectrum ß-lactamases in Colombian clinical isolates of non-typhoidal Salmonella enterica between 1997 and 2022

Introducción. Salmonella spp. es un agente patógeno zoonótico transmitido al humano por el agua o los alimentos contaminados. La presencia de ß-lactamasas de espectro extendido es un creciente problema para la salud pública debido a que estas enzimas confieren resistencia contra las cefalosporinas de tercera y cuarta generación. Objetivo. Caracterizar las ß-lactamasas de espectro extendido en aislamientos de Salmonella spp. recibidos por el programa de vigilancia de enfermedad diarreica aguda o enfermedad transmitida por alimentos del Grupo de Microbiología del Instituto Nacional de Salud. Materiales y métodos. Entre enero de 1997 y junio de 2022, se recibieron 444 aislamientos de Salmonella spp. resistentes, por lo menos, a una de las cefalosporinas de tercera generación. El fenotipo de las ß-lactamasas de espectro extendido se identificó con la prueba de doble disco. El ADN se extrajo por ebullición y mediante PCR se amplificaron los genes bla CTX-M, bla SHVy : ' a ILM. Resultados. Todos los aislamientos fueron positivos para la prueba de ß-lactamasas de espectro extendido. Los resultados de la amplificación por PCR fueron: bla CTX-M + bla TLM (n=200), bla CTX-M (n=177), bla SHV(n=16), bla SHV + bla CTX-M (n=6), bla TLM (n=13) y bla SHV + bla CTX-M + bla TLM (n=3). Del total, 26 aislamientos fueron negativos para los genes evaluados. Los aislamientos positivos para ß-lactamasas de espectro extendido se identificaron en Bogotá y en 21 departamentos: Chocó, Magdalena, Meta, Bolívar, Casanare, Cesar, Córdoba, Quindío, Atlántico, Tolima, Cauca, Cundinamarca, Huila, Boyacá, Caldas, Norte de Santander, Risaralda, Antioquia, Nariño, Santander y Valle del Cauca. Conclusión. La resistencia a las cefalosporinas de tercera generación en aislamientos de Salmonella spp. fue generada principalmente por bla CTX-M. El 44 % (197/444) de los aislamientos presentó resistencia a ampicilina, tetraciclina, cloranfenicol y trimetoprim- sulfametoxazol Los serotipos portadores de ß-lactamasas de espectro extendido más frecuentes fueron S. Typhimurium y S. Infantis.

Introduction. Salmonella spp. is a zoonotic pathogen transmitted to humans through contaminated water or food. The presence of extended-spectrum ß-lactamases is a growing public health problem because these enzymes are resistant to third and fourth generation cephalosporins. Objective. To characterize extended-spectrum ß-lactamases in Salmonella spp. isolates received by the acute diarrheal disease/foodborne disease surveillance program of the Grupo de Microbiología of the Instituto Nacional de Salud. Materials and methods. A total of 444 Salmonella spp. isolates, resistant to at least one of the cephalosporins, were obtained between January 1997 and June 2022. The extended- spectrum ß-lactamases phenotype was identified by the double disk test. DNA extraction was carried out by the boiling method, and the bla CTX-M, bla SHV, and bla TLM genes were amplified by PCR. Results. All the isolates were positive for the extended-spectrum ß-lactamases test. The genes identified were: bla CTX-M + ba TLM (n=200), bla CTX-M (n=177), bla SHV(n=16), bla SHV + bla CTX-M (n=6), bla TLM (n=13) and bla SHV + bla CTX-M + bla TLM (n=3). Twenty-six isolates were negative for the evaluated genes. Positive extended-spectrum ß-lactamases isolates were identified in Bogotá and 21 departments: Chocó, Magdalena, Meta, Bolívar, Casanare, Cesar, Córdoba, Quindío, Atlántico, Tolima, Cauca, Cundinamarca, Huila, Boyacá, Caldas, Norte de Santander, Risaralda, Antioquia, Nariño, Santander y Valle del Cauca. Conclusion. Resistance to third generation cephalosporins in Salmonella spp. isolates was mainly caused by bla CTX-M. Isolates were resistant to ampicillin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole (44 %; 197/444). The most frequent extended-spectrum ß-lactamases-expressing serotypes were Salmonella Typhimurium and Salmonella Infantis.

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND: The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS: For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS: Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION: COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING: Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization.

Demographic and clinical risk factors associated with severity of lab-confirmed human leptospirosis in Colombia, 2015-2020.

BACKGROUND: Leptospirosis is a common zoonoses and is a major global public health threat. Most cases are mild, typically presenting as a non-specific acute febrile illness. However, leptospirosis can have life-threatening manifestations, including pulmonary hemorrhage syndrome, and acute kidney injury. In Colombia, notification and lab-confirmation of suspected human cases are mandatory. However, little is known about the demographic and clinical factors associated with severe leptospirosis, which could help to reduce clinical complications and mortality. Our aim was to identify risk factors associated with severe leptospirosis, intensive care unit (ICU) admission, and mortality in lab-confirmed cases in Colombia, 2015-2020. METHODS AND FINDINGS: We analyzed 201 lab-confirmed human leptospirosis cases by microagglutination test. We used a logistic regression to identify the demographic and clinical risk factors associated with severe leptospirosis, admission to ICU, and death. Most leptospirosis confirmed cases occurred in men (85.6%); the mean age was 36.7 years. We classified severe cases (43.3%) by clinical manifestations as renal (29.9%) and liver (27.4%) failure, multiple-organ failure (24.4%), septic shock (24.4%), Weil syndrome (18.4%), pulmonary hemorrhage (18.4%), and meningitis (2.5%), admitted to the ICU (30.3%), and fatal (8.5%). Clinical conditions associated with severe leptospirosis were dyspnea (OR: 5.54; 95% CI: 1.46 to 20.98), tachycardia (OR:9.69; 95% CI: 15.96 to 58.8), and rash (OR: 10.25; 95% CI: 25.01 to 42.08). CONCLUSIONS: We identified demographic characteristics and clinical symptoms associated with severe leptospirosis in Colombia. We hope these results can support clinicians in providing timely treatment to leptospirosis patients to avoid preventable medical complications or deaths.

An Alzheimer's disease risk variant in TTC3 modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons.

A missense variant in the tetratricopeptide repeat domain 3 ( TTC3 ) gene (rs377155188, p.S1038C, NM_003316.4:c.3113C>G) was found to segregate with disease in a multigenerational family with late onset Alzheimer's disease. This variant was introduced into induced pluripotent stem cells (iPSCs) derived from a cognitively intact individual using CRISPR genome editing and the resulting isogenic pair of iPSC lines were differentiated into cortical neurons. Transcriptome analysis showed an enrichment for genes involved in axon guidance, regulation of actin cytoskeleton, and GABAergic synapse. Functional analysis showed that the TTC3 p.S1038C iPSC-derived neuronal progenitor cells had altered 3D morphology and increased migration, while the corresponding neurons had longer neurites, increased branch points, and altered expression levels of synaptic proteins. Pharmacological treatment with small molecules that target the actin cytoskeleton could revert many of these cellular phenotypes, suggesting a central role for actin in mediating the cellular phenotypes associated with the TTC3 p.S1038C variant. Highlights: The AD risk variant TTC3 p.S1038C reduces the expression levels of TTC3 The variant modifies the expression of AD specific genes BACE1 , INPP5F , and UNC5C Neurons with the variant are enriched for genes in the PI3K-Akt pathwayiPSC-derived neurons with the alteration have increased neurite length and branchingThe variant interferes with actin cytoskeleton and is ameliorated by Cytochalasin D.

Infections in patients with adverse reactions to the use of unknown modeling substances for soft tissue enhancement in Cali, Colombia.

The infiltration of foreign materials not approved for medical purposes or of modeling substances used in soft tissue to modify the anatomical appearance for aesthetic purposes represents a serious health problem. These procedures lead to the development of delayed complications, including infections. The objective of this study was to characterize infections in patients with adverse reactions to the use of modeling substances in Cali, Colombia. A cross-sectional and descriptive study was used to determine the frequency of bacterial and fungal infections associated with complications from and adverse reactions to the use of modeling substances in 113 patients. We identified microorganisms in 22 patients and a frequency of 68.1% monomicrobial infections and 31.8% polymicrobial infections. The microorganisms identified in our study included Bacillus cereus, Mycobacterium fortuitum, and Pseudomonas stutzeri, among other microorganisms. The presence of adverse effects derived from the use of illegal modeling substances has been demonstrated; among these effects, infections occur with high frequency and place the health of the patient at risk and increase problems in health care.

Population structure of Neisseria meningitidis ST-9493 identified in Colombian isolates.

INTRODUCTION: Neisseria meningitidis is associated with invasive infections causing high mortality rates. The objective of this study was to describe the population structure of Colombian invasive isolates with ST-9493, a potentially emerging clonal group in the country. METHODS: The complete genomes of 34 invasive isolates of serogroup B with ST-9493 and its variants at one or two loci were sequenced by Illumina to describe the phenotypic and genotypic characteristics of these isolates. RESULTS: The relationship of a clonal group associated with ST-136 CC41/44 was phylogenetically established, identifying two main clades composed of isolates from an outbreak or endemic. The most frequent alleles and peptides included porA 17, porB 44, fHbp 2.24, NHBA 10, and the FetA F5-17 variant. Most of the isolates were susceptible to the antibiotics evaluated. CONCLUSION: This study shows that meningococcal isolates with ST-9493 are an autochthonous clonal group with population dynamics and the capacity to cause endemic and epidemic meningococcal disease in Colombia.

Crosstalk between dihydroceramides produced by Porphyromonas gingivalis and host lysosomal cathepsin B in the promotion of osteoclastogenesis.

Emerging studies indicate that intracellular eukaryotic ceramide species directly activate cathepsin B (CatB), a lysosomal-cysteine-protease, in the cytoplasm of osteoclast precursors (OCPs) leading to elevated RANKL-mediated osteoclastogenesis and inflammatory osteolysis. However, the possible impact of CatB on osteoclastogenesis elevated by non-eukaryotic ceramides is largely unknown. It was reported that a novel class of phosphoglycerol dihydroceramide (PGDHC), produced by the key periodontal pathogen Porphyromonas gingivalis upregulated RANKL-mediated osteoclastogenesis in vitro and in vivo. Therefore, the aim of this study was to evaluate a crosstalk between host CatB and non-eukaryotic PGDHC on the promotion of osteoclastogenesis. According to a pulldown assay, high affinity between PGDHC and CatB was observed in RANKL-stimulated RAW264.7 cells in vitro. It was also demonstrated that PGDHC promotes enzymatic activity of recombinant CatB protein ex vivo and in RANKL-stimulated osteoclast precursors in vitro. Furthermore, no or little effect of PGDHC on the RANKL-primed osteoclastogenesis was observed in male and female CatB-knock out mice compared with their wild type counterparts. Altogether, these findings demonstrate that bacterial dihydroceramides produced by P. gingivalis elevate RANKL-primed osteoclastogenesis via direct activation of intracellular CatB in OCPs.