Listeria brain abscess: a therapeutically challenging rare presentation of listeriosis.

We report a very rare case of Listeria multiple brain abscesses manifested as delirium, which represented diagnostic and therapeutic challenges overcome only by the close cooperation between Infectious Diseases and Neuroradiology, without which a satisfactory outcome would not be achieved.An elderly man presented with confusion and drowsiness with a background of type-II diabetes mellitus. Although computed tomography of the brain only showed frontal lobe oedema, contrast magnetic resonance (MR) imaging showed numerous irregular rim-enhancing lesions containing central diffusion restriction, suggesting multiple pyogenic cerebral abscesses of unclear aetiology. Thereafter, Listeria monocytogenes was isolated from blood cultures, suggesting this as the causative organism. Deemed unsuitable for neurosurgical drainage, the patient received medical management with a protracted course of antibiotics. This case was extremely challenging, due to 1) the impossibility of source control, 2) the small number of effective antibiotics available to treat this condition, and 3) the inevitable antibiotic side-effects, derived from long-term exposure. A successful outcome was only possible thanks to strict close multidisciplinary follow up, requiring frequent MR imaging and a judicious antibiotic choice, including monitoring of their side-effects. Due to the rarity of this condition, there is lack of guidance on its management, hence the importance of multidisciplinary involvement with very close imaging and antibiotic monitoring.

RNA molecules display distinctive organization at nuclear speckles.

RNA molecules often play critical roles in assisting the formation of membraneless organelles in eukaryotic cells. Yet, little is known about the organization of RNAs within membraneless organelles. Here, using super-resolution imaging and nuclear speckles as a model system, we demonstrate that different sequence domains of RNA transcripts exhibit differential spatial distributions within speckles. Specifically, we image transcripts containing a region enriched in binding motifs of serine/arginine-rich (SR) proteins and another region enriched in binding motifs of heterogeneous nuclear ribonucleoproteins (hnRNPs). We show that these transcripts localize to the outer shell of speckles, with the SR motif-rich region localizing closer to the speckle center relative to the hnRNP motif-rich region. Further, we identify that this intra-speckle RNA organization is driven by the strength of RNA-protein interactions inside and outside speckles. Our results hint at novel functional roles of nuclear speckles and likely other membraneless organelles in organizing RNA substrates for biochemical reactions.

Extrapulmonary nontuberculous mycobacterial infections: a guide for the general physician.

Non-tuberculous mycobacteria (NTM) infections predominantly present as pulmonary disease. Although relatively rare, 20-30 % originate from extrapulmonary sites resulting in a wide range of clinical syndromes. Immunocompromised individuals are particularly susceptible. Clinical manifestations include skin and soft-tissue infections, lymphadenitis, musculoskeletal infections and disseminated disease. Diagnosing extrapulmonary NTM is challenging, and management is complex, often involving multiple radiological and microbiological investigations, long courses of combination antibiotic regimens and may require adjuvant surgical interventions. We highlight both the importance of involving NTM experts at an early stage and the role of a multidisciplinary approach in the diagnosis and management of these infections.

Psychopathological Risk in Siblings of Subjects with Attention-Deficit/Hyperactivity Disorder: A cross-Sectional Study.

OBJECTIVE: We aim to determine the prevalence of mental disorders in siblings of children with attention deficit hyperactivity disorder (ADHD), and to determine how psychosocial adversity factors relate to this psychopathology, in a low-middle income country (Colombia). METHODS: We evaluated subjects with ADHD diagnosed according to the DSM-5 criteria, one of their parents and one of their siblings (ages 8-19). We used the ADHD rating scale and a set of instruments to assess the presence of mental disorders as well as psychosocial adversity. RESULTS: We evaluated 74 trios formed by the index case with ADHD, one sibling and one of the parents. We found that 24.3% of the participating siblings also met the criteria for ADHD and another 24.3% for other psychiatric disorders. The risk of these siblings having ADHD increased further when one of the parents reported a history of ADHD. We also found that 28.3% of the families faced high levels of psychosocial adversity as per their scores in the Rutter Adversity Index. CONCLUSIONS: Siblings of subjects with ADHD showed a significant risk for ADHD and other mental disorders. That risk increased if a parent reported a history of ADHD and also when two or more psychosocial adversity factors were present. This study supports the importance of early detection in efforts to decrease the risk for other siblings.

Engineered transcription-associated Cas9 targeting in eukaryotic cells.

DNA targeting Class 2 CRISPR-Cas effector nucleases, including the well-studied Cas9 proteins, evolved protospacer-adjacent motif (PAM) and guide RNA interactions that sequentially license their binding and cleavage activities at protospacer target sites. Both interactions are nucleic acid sequence specific but function constitutively; thus, they provide intrinsic spatial control over DNA targeting activities but naturally lack temporal control. Here we show that engineered Cas9 fusion proteins which bind to nascent RNAs near a protospacer can facilitate spatiotemporal coupling between transcription and DNA targeting at that protospacer: Transcription-associated Cas9 Targeting (TraCT). Engineered TraCT is enabled when suboptimal PAM interactions limit basal activity in vivo and when one or more nascent RNA substrates are still tethered to the actively transcribing target DNA in cis. We further show that this phenomenon can be exploited for selective editing at one of two identical targets in distinct gene loci, or, in diploid allelic loci that are differentially transcribed. Our work demonstrates that temporal control over Cas9's targeting activity at specific DNA sites may be engineered without modifying Cas9's core domains and guide RNA components or their expression levels. More broadly, it establishes RNA binding in cis as a mechanism that can conditionally stimulate CRISPR-Cas DNA targeting in eukaryotes.

Psychopathological Risk in Siblings of Subjects with Attention-Deficit/Hyperactivity Disorder: A cross-Sectional Study

Objective: We aim to determine the prevalence of mental disorders in siblings of children with attention deficit hyperactivity disorder (ADHD), and to determine how psychosocial adversity factors relate to this psychopathology, in a low-middle income country (Colombia). Methods: We evaluated subjects with ADHD diagnosed according to the DSM-5 criteria, one of their parents and one of their siblings (ages 8-19). We used the ADHD rating scale and a set of instruments to assess the presence of mental disorders as well as psychosocial adversity. Results: We evaluated 74 trios formed by the index case with ADHD, one sibling and one of the parents. We found that 24.3% of the participating siblings also met the criteria for ADHD and another 24.3% for other psychiatric disorders. The risk of these siblings having ADHD increased further when one of the parents reported a history of ADHD. We also found that 28.3% of the families faced high levels of psychosocial adversity as per their scores in the Rutter Adversity Index. Conclusions: Siblings of subjects with ADHD showed a significant risk for ADHD and other mental disorders. That risk increased if a parent reported a history of ADHD and also when two or more psychosocial adversity factors were present. This study supports the importance of early detection in efforts to decrease the risk for other siblings.

Objetivo: Nuestro objetivo es determinar la prevalencia de trastornos mentales en hermanos de casos con TDAH y cómo los factores de adversidad psicosocial se relacionan con esta psicopatología en un país de ingresos bajos-medios (Colombia). Métodos: Se evaluó a sujetos con TDAH diagnosticado según los criterios del DSM-5, uno de sus padres y uno de sus hermanos (edades, 8-19 anos). Mediante la escala de calificación del TDAH y un conjunto de otros instrumentos se evaluó la presencia de trastornos mentales y adversidad psicosocial. Resultados: Se evaluó a 74 tríos formados por el caso índice con TDAH, un hermano y uno de los padres. Se halló que un 24,3% de los hermanos participantes también cumplían los criterios de TDAH y otro 24,3%, otros trastornos psiquiátricos. El riesgo de que estos hermanos tuvieran TDAH aumentó aún más cuando uno de los padres informó antecedentes de TDAH. También, que el 28,3% de las familias se enfrentaron a altos niveles de adversidad psicosocial según sus puntuaciones en el Índice de Adversidad de Rutter. Conclusiones: Los hermanos de sujetos con TDAH mostraron un significativo riesgo de TDAH y otros trastornos mentales. Ese riesgo aumenta si uno de los padres reporta antecedentes de TDAH y también cuando se presentan 2 o más factores de adversidad psicosocial. Este estudio respalda la importancia de la detección temprana con el fin de disminuir el riesgo para otros hermanos.

Clinical, microbiological characteristics and predictors of mortality in patients with carbapenemase-producing Enterobacterales bloodstream infections: a multicentre study.

Objectives: To investigate the clinical, microbiological characteristics and outcomes of patients with bloodstream infections (BSI) due to carbapenemase-producing Enterobacterales (CPE). Methods: A multicentre retrospective observational study of patients with BSIs due to CPE admitted to six UK hospitals was conducted between 2011 and 2021. Multivariate analysis was used to identify factors predicting 30-day case fatality rate (CFR). Results: There were 84 episodes of CPE-BSIs, 37 (44%) due to OXA-48, 35 (42%) to metallo-betalactamases (MBL) and 12 (14%) to KPC. 63% of patients were male with a median age of 64 years. Common organisms included Klebsiella spp. (61%), Escherichia coli (20%) and Enterobacter spp. (13%). Urinary devices were more often involved in OXA-48 BSIs (12/37; 32%) compared to infections caused by MBL and KPC (4/35; 11% and 1/12; 8%; P = 0.046). In contrast, central venous catheters were more frequently present in KPC-BSIs (10/12; 92%) compared with OXA-48 and MBL (11/37; 30% and 20/35; 57%; P = 0.002). Effective definitive antimicrobials were received by 72/84 (86%) patients, comprising monotherapy (32/72; 44%) or combination therapy (40/72; 56%). 30-day case fatality rate (CFR) was 38%. Sepsis or septic shock was associated with death [OR 3.81 (CI 1.19-12.14), P = 0.024]. Conclusion: Strategies targeting high-risk patients and adherence to infection prevention bundles for urinary devices and central venous catheters can reduce OXA-48 and KPC-BSIs. Early recognition and management of severe sepsis, prompt initiation of appropriate antimicrobial therapy and development of novel antimicrobials are crucial to mitigate the high CFR associated with CPE-BSIs.

Gonococcal pericarditis with tamponade - use of molecular technology to improve diagnosis and management.

We report a case of gonococcal pericarditis, which was unexpected due to its extremely unusual occurrence. A 42-year-old man presented with fever, chest pain, dyspnea, and tachycardia. He was initially stable but rapidly deteriorated, developing pericardial effusion with tamponade requiring a pericardial window. Incompletely decolorized gram stain of the pericardial fluid initially suggested the presence of gram-positive diplococci, which wrongly directed treatment toward possible pneumococcal infection. Because cultures were negative, identification of the causative organism was attempted by molecular and genotyping analysis. These techniques identified Neisseria gonorrhoeae-multi-antigen sequence type 14994 (por 5136/tbpB 33) as the etiology, which has been associated with disseminated gonococcal disease. Real-time polymerase chain reaction showed no evidence of mutations within the N. gonorrhoeae penA gene responsible for causing ceftriaxone resistance. This was crucial in guiding antibiotic treatment, in light of the high prevalence of multi-drug-resistant N. gonorrhoeae. This case highlights the utility of diagnostic molecular techniques in identifying N. gonorrhoeae as the etiology of an exceedingly rare case of pericarditis.

Characteristics and fate of plastic pollution in urban stormwater ponds.

Stormwater runoff is often assumed to be an important pathway for microplastics from the terrestrial to the marine environment, although few studies have attempted to quantify the significance of this pathway or the interactions between stormwater infrastructure and plastic pollution. The objective of this study was to determine what factors influence the concentrations and behaviors of microplastics in stormwater ponds. Samples were taken from the water and bottom sediments of six stormwater ponds in Tampa (Florida, USA) using a neuston net and a sediment dredger. They were processed using a combination of density separations, visual sorting, and Raman spectroscopy. Concentrations ranged by several orders of magnitude between sites and rounds of sampling (0.0-55.5 items/m3 in water, 2.5-203.0 items/kg dry weight in sediment) but were comparable to other studies. The sediments of fenced and residential sites had significantly lower plastic count concentrations, compared to unfenced sites with mixed land uses. The ratio of impervious drainage area to pond surface area was found to be positively correlated with sediment concentrations. Particle shapes in water were more variable than those found in sediments, suggesting that regular-shaped plastics tend to settle first. Circularity was identified as an important parameter in determining settling behaviors. Shape characteristics were similar to those observed in a downstream river, suggesting that degradation leading to the observed shapes occurred prior to entering the ponds. This study highlights the importance of stormwater infrastructure in understanding plastic transport and how plastic shape characteristics can impact their behavior in the environment.

Are the concepts of emotion special? A comparison between basic-emotion, secondary-emotion, abstract, and concrete words.

The study of emotional concepts stands at a very interesting intersection between the theoretical debate about the nature of emotions and the debate about the nature of processing concrete concepts and abstract concepts. On the one hand, it is debated whether it is possible to differentiate basic emotions from secondary emotions and, on the other hand, whether emotional concepts differ from abstract concepts. In this regard, the prototypical perceptual aspects are considered an important factor both for the differentiation between concrete and abstract concepts and for the differentiation between basic and secondary emotions (facial expressions). Thus, the objective has been to determine if (a) the presence or absence of a prototypical perceptual referent, and (b) the type of concept (referring to emotion and not referring to emotion), produce differences between concepts of basic emotions, secondary emotions and concepts not related to emotions, concrete and abstract, in the tasks of qualification of concreteness, imageability and availability of context and the task of the list of properties, that have been used in previous studies. A total of 86 university students from the suburbs of La Serena - Coquimbo (Chile), all native Spanish speakers, participated in the study. The results show that in the perception of concreteness and in the total of enumerated properties, emotional concepts presented similar results to abstract concepts not related to emotion and there was no difference between basic and secondary emotion concepts. In imageability and context availability, emotional concepts were perceived as different from and more concrete than abstract concepts. In addition, the cause-effect type attributes allowed to clearly differentiate emotional concepts from those not related to emotion and to differentiate between basic and secondary emotion concepts. These types of attributes appear almost exclusively in emotional concepts and are more frequent in basic emotions. These results are partially consistent with the predictions of Neurocultural and Conceptual Act theories about emotions.

The Use of a Suprascapular Nerve Block to Facilitate the Reduction of an Anterior Shoulder Dislocation: An Alternative for Elderly and Patients With Cardiopulmonary Comorbidities?

BACKGROUND: Anterior shoulder dislocation is a common presentation to the emergency department (ED). Dislocations are spontaneous or traumatic. Generally, a reduction is performed under procedural sedation and analgesia (PSA). Other approaches include the use of intra-articular lidocaine or, in rare instances, nerve blocks. Here we discuss the case of a 66-year-old female patient who presented with left shoulder pain and limited range of motion after a fall. After discussing potential treatment options to reduce the dislocation, the patient agreed to a nerve block. DISCUSSION: The dislocation was reduced successfully with a suprascapular nerve block (SSNB) without complications. The duration of the patient's ED stay was shorter than those who had received PSA. CONCLUSIONS: SSNB could be an alternative method for shoulder dislocation reduction, particularly for patients who are obese, older, or have cardiopulmonary comorbidities.

Semi-empirical quantum optics for mid-infrared molecular nanophotonics.

Nanoscale infrared (IR) resonators with sub-diffraction limited mode volumes and open geometries have emerged as new platforms for implementing cavity quantum electrodynamics at room temperature. The use of IR nanoantennas and tip nanoprobes to study strong light-matter coupling of molecular vibrations with the vacuum field can be exploited for IR quantum control with nanometer spatial and femtosecond temporal resolution. In order to advance the development of molecule-based quantum nanophotonics in the mid-IR, we propose a generally applicable semi-empirical methodology based on quantum optics to describe light-matter interaction in systems driven by mid-IR femtosecond laser pulses. The theory is shown to reproduce recent experiments on the acceleration of the vibrational relaxation rate in infrared nanostructures. It also provides physical insights on the implementation of coherent phase rotations of the near-field using broadband nanotips. We then apply the quantum framework to develop general tip-design rules for the experimental manipulation of vibrational strong coupling and Fano interference effects in open infrared resonators. We finally propose the possibility of transferring the natural anharmonicity of molecular vibrational levels to the resonator near-field in the weak coupling regime to implement intensity-dependent phase shifts of the coupled system response with strong pulses and develop a vibrational chirping model to understand the effect. The semi-empirical quantum theory is equivalent to first-principles techniques based on Maxwell's equations, but its lower computational cost suggests its use as a rapid design tool for the development of strongly coupled infrared nanophotonic hardware for applications ranging from quantum control of materials to quantum information processing.

Optimizing Amazonian dams for nature.

Algorithms assess opportunities, forgone benefits, and environmental trade-offs.

Coupled CH4 production and oxidation support CO2 supersaturation in a tropical flood pulse lake (Tonle Sap Lake, Cambodia).

Carbon dioxide (CO2) supersaturation in lakes and rivers worldwide is commonly attributed to terrestrial-aquatic transfers of organic and inorganic carbon (C) and subsequent, in situ aerobic respiration. Methane (CH4) production and oxidation also contribute CO2 to freshwaters, yet this remains largely unquantified. Flood pulse lakes and rivers in the tropics are hypothesized to receive large inputs of dissolved CO2 and CH4 from floodplains characterized by hypoxia and reducing conditions. We measured stable C isotopes of CO2 and CH4, aerobic respiration, and CH4 production and oxidation during two flood stages in Tonle Sap Lake (Cambodia) to determine whether dissolved CO2 in this tropical flood pulse ecosystem has a methanogenic origin. Mean CO2 supersaturation of 11,000 ± 9,000 µatm could not be explained by aerobic respiration alone. 13C depletion of dissolved CO2 relative to other sources of organic and inorganic C, together with corresponding 13C enrichment of CH4, suggested extensive CH4 oxidation. A stable isotope-mixing model shows that the oxidation of 13C depleted CH4 to CO2 contributes between 47 and 67% of dissolved CO2 in Tonle Sap Lake. 13C depletion of dissolved CO2 was correlated to independently measured rates of CH4 production and oxidation within the water column and underlying lake sediments. However, mass balance indicates that most of this CH4 production and oxidation occurs elsewhere, within inundated soils and other floodplain habitats. Seasonal inundation of floodplains is a common feature of tropical freshwaters, where high reported CO2 supersaturation and atmospheric emissions may be explained in part by coupled CH4 production and oxidation.