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Background: The collection of blood cultures (BC) is key for guiding antimicrobial therapy in children with febrile neutropenia (FN), more than 90% have central venous catheters (CVC). There is no consensus on the need for peripheral BC over central BC in this population. The aim of this study was to determine the contribution of peripheral BC over central BC in the diagnosis of bloodstream infections in children with FN., Methods: Descriptive, retrospective study, episodes of FN recorded prospectively in 6 hospitals in Santiago, Chile, from 2016 to 2021. Central and peripheral BC were drawn upon admission. All episodes with at least one (+) BC were allocated to one of these groups: consistent (+) BC, inconsistent (+) BC, only CVC (+) BC and only peripheral (+) BC. The volume of the samples was recorded., Results: The analysis included 241 episodes of FN with at least one (+) BC. The median age was 7.2 years, 51% were female, 84% had hematological cancer and 98% had episodes of high-risk FN. Of a total of 241 episodes, 135 (56%) had consistent (+) BC, 13 (5%) had inconsistent (+) BC, 35 (15%) had only CVC (+) BC and 58 (24%) had only peripheral (+) BC. There were no significant differences in the volume of the samples between central and peripheral BC., Conclusions: The proportion of bloodstream infections detected only through peripheral BC was 24%, higher than previously reported, not due to sample volume. We recommend obtaining peripheral as well CVC BC in children with FN., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

To reproduce and to transmit disease, female mosquitoes must obtain blood meals and locate appropriate sites for egg laying (oviposition). While distinct sensory cues drive each behavior, humidity contributes to both. Here, we identify the mosquito's humidity sensors (hygrosensors). Using generalizable approaches designed to simplify genetic analysis in non-traditional model organisms, we demonstrate that the ionotropic receptor Ir93a mediates mosquito hygrosensation as well as thermosensation. We further show that Ir93a-dependent sensors drive human host proximity detection and blood-feeding behavior, consistent with the overlapping short-range heat and humidity gradients these targets generate. After blood feeding, gravid females require Ir93a to seek high humidity associated with preferred egg-laying sites. Reliance on Ir93a-dependent sensors to promote blood feeding and locate potential oviposition sites is shared between the malaria vector Anopheles gambiae and arbovirus vector Aedes aegypti. These Ir93a-dependent systems represent potential targets for efforts to control these human disease vectors., Competing Interests: Declaration of interests P.A.G. is a co-inventor on patent WO2017196861A1 (WIPO PCT; pending; inventors: Z. Knecht, P. Garrity, L. Ni) “Methods for modulating insect hygro- and/or thermosensation.” This patent proposes using members of the ionotropic receptor family as targets for strategies to disrupt hygro- and thermo-sensation in insects. W.J.L. and P.A.G. are co-inventors on patent application PCT/US2021/052374, “Sterile organisms, methods of making, and methods of use thereof.” This patent includes methods for genetic manipulations in non-traditional model organisms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mosquito-borne diseases such as malaria, Zika virus, and dengue virus are a menace to the human population. Although many mosquito species are not attracted to humans and do not feed on blood, human-biting female mosquitoes are strongly attracted to people and use chemosensory cues to identify a suitable host for a blood meal. Mosquitoes need blood components to reproduce, rendering them excellent vectors for blood-borne diseases. The three genera ( Culex , Anopheles , and Aedes ) responsible for most of these diseases find hosts by using their peripheral sensory organs. These organs include the antennae, maxillary palps, and proboscis. All three contain diverse populations of highly sensitive neurons that express sensory receptors that can detect odorants, temperature, chemicals, and tastants. Although these organs are essential to the host-seeking behavior that results in biting, their small size and thick outer cuticle can hinder typical histochemical analyses. Here, we briefly review the role the peripheral sensory organs play in mosquito behavior. Then, we introduce how to investigate their gene expression profiles using immunohistochemical and RNA in situ approaches for both whole-mount and frozen-section preparations., (© 2023 Cold Spring Harbor Laboratory Press.)

Immunohistochemistry analysis of mosquitoes is complicated by the outer cuticle that prevents reagents from penetrating peripheral tissues. This protocol incorporates a cryosectioning method that provides a higher resolution of the internal architecture of mosquito peripheral sensory tissues and enables the visualization of protein expression. This eliminates the need for enzymatic steps to digest the outer cuticle that encases these tissues. This protocol can also be adapted for other tissues, such as the brain and the legs, as chitin exoskeleton thickness does not affect antibody penetration once the sample is sectioned., (© 2023 Cold Spring Harbor Laboratory Press.)

Purpose: In response to the spread of COVID-19 in Switzerland, ophthalmology practices implemented a variety of preventive measures in order to minimise the risk of contamination to their patients and staff. Yet, some studies suggested that over a quarter of all glaucoma patients never returned to the clinic after the first lockdown eased. This raises the question of the factors influencing Patients' likelihood to keep their appointments in this COVID-19 era. The aim of this study was therefore to assess ophthalmology Patients' perception of COVID-19 preventive measures, as well as their impact on glaucoma Patients' clinic attendance and follow-up., Methods: This was a prospective study based on primary data collected from 12 private ophthalmology clinics in French-speaking Switzerland. A web-based patient experience questionnaire was designed to assess Patients' appreciation of the preventive measures in place at their eye care provider as well as their intention to attend further follow-up appointments. These measures were made on modified 10-point Likert scales. Every patient who attended an appointment at one of the participating clinics on randomly selected dates in October 2020 was offered voluntary enrolment into the study., Results: In all, 118 surveys were completed and analysed. The mean age of respondents was 57.8 ± 18.0 years, 59.3% were female, and 71.2% were Swiss nationals. Fifty-four (45.8%) of them suffered from glaucoma. Overall, patients were highly satisfied with the measures in place to safeguard them from COVID-19 infection, with a mean score of 9.29 ± 1.35. This was higher amongst Swiss nationals (9.55 ± 0.77) than foreigners (8.65 ± 2.09). On average, responders expressed a 90.2 ± 17.5 percent likelihood to keep their follow-up appointment. The figure went down to 88.5 ± 19.9 percent amongst glaucoma patients (p = 0.58), and 86.3 ± 22.1 percent amongst glaucoma patients aged 65 and over (p = 0.29). Interestingly, older glaucoma Patients' satisfaction with preventive measures in place strongly correlated with their likelihood to keep follow-up appointments (r = 0.72). The correlation was moderate amongst all glaucoma patients (r = 0.46) and weak amongst all respondents (r = 0.38) and those over 65 (r = 0.44)., Conclusions: The present research highlights the importance of Patients' perception on COVID-19 preventive measures in place in ophthalmology clinics, which was directly associated with their likelihood to keep follow-up appointments. Vulnerable subgroups of patients were more likely to miss their follow-up appointments altogether, and their decision to attend was more strongly influenced by their perceived risk of contracting COVID-19. This suggests a role for telemedicine in more vulnerable patients suffering from progressive diseases such as glaucoma., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Mosquitoes transmit pathogens that kill >700,000 people annually. These insects use body heat to locate and feed on warm-blooded hosts, but the molecular basis of such behavior is unknown. Here, we identify ionotropic receptor IR21a, a receptor conserved throughout insects, as a key mediator of heat seeking in the malaria vector Anopheles gambiae Although Ir21a mediates heat avoidance in Drosophila , we find it drives heat seeking and heat-stimulated blood feeding in Anopheles At a cellular level, Ir21a is essential for the detection of cooling, suggesting that during evolution mosquito heat seeking relied on cooling-mediated repulsion. Our data indicate that the evolution of blood feeding in Anopheles involves repurposing an ancestral thermoreceptor from non-blood-feeding Diptera., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

While transcriptional controls over the size and relative position of cortical areas have been identified, less is known about regulators that direct acquisition of area-specific characteristics. Here, we report that the transcription factor Ctip1 functions in primary sensory areas to repress motor and activate sensory programs of gene expression, enabling establishment of sharp molecular boundaries defining functional areas. In Ctip1 mutants, abnormal gene expression leads to aberrantly motorized corticocortical and corticofugal output connectivity. Ctip1 critically regulates differentiation of layer IV neurons, and selective loss of Ctip1 in cortex deprives thalamocortical axons of their receptive "sensory field" in layer IV, which normally provides a tangentially and radially defined compartment of dedicated synaptic territory. Therefore, although thalamocortical axons invade appropriate cortical regions, they are unable to organize into properly configured sensory maps. Together, these data identify Ctip1 as a critical control over sensory area development., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A temperature-sensitive receptor prevents mosquitoes from being attracted to targets that are hotter than a potential host.

Introduction: Ruminants are regarded as the natural reservoir for Shiga toxin-producing Escherichia coli (STEC), especially of serogroup O157., Materials and Methods: During 2011 and 2012, 320 samples (160 faecal samples from the rectum and 160 hide samples from the brisket area) were collected from 160 cattle at slaughter in Northern Italy during warm months (May to October). Cattle were reared in different farms and their age at slaughter ranged between nine months and 15 years, most of them being culled cattle (median age: six years; average age: 4.6 years). Samples were tested by immunomagnetic-separation technique for E coli O157 and O26 and by a screening PCR for stx genes followed by cultural detection of STEC. The virulence genes stx1, stx2, eae, and e-hlyA were detected and among stx2-positive isolates the presence of the stx2a and stx2c variants was investigated., Results: Twenty-one of 160 cattle (13.1 per cent; 95 per cent CI 8.3 to 19.4 per cent) were found to be faecal carriers of STEC. STEC O157 was found in 10 (6.3 per cent) samples, STEC O26 in six (3.8 per cent) and STEC O111 in one (0.6 per cent). Four isolates (2.5 per cent) were O not determined (OND). Six out of 160 (3.8 per cent; 95 per cent CI 1.4 to 8.0 per cent) hide samples were positive for STEC; four hides (2.5 per cent) were contaminated by STEC O157 and two (1.3 per cent) by STEC O26. In three cattle (1.9 per cent) STEC from both faeces and hides were detected. Among STEC O157, 87.5 per cent of them carried the stx2c gene and 12.5 per cent carried both stx1 and stx2c genes. No O157 isolate harboured stx2a variant. STEC O26 and O111 carried the stx1 gene only. One OND strain carried both the stx2a and stx2c genes., Conclusions: This study shows that STEC O157 from cattle can harbour the stx2c variant, which is associated with haemolytic uraemic syndrome in humans, and that cattle hides may be a source of human pathogenic STEC O157 and O26 in the slaughterhouse environment.

Activin receptor-like kinase 1 (ALK1), an endothelial cell-specific type I receptor of the TGF-β superfamily, is an important regulator of normal blood vessel development as well as pathological tumor angiogenesis. As such, ALK1 is an important therapeutic target. Thus, several ALK1-directed agents are currently in clinical trials as anti-angiogenic cancer therapeutics. Given the biological and clinical importance of the ALK1 signaling pathway, we sought to elucidate the biophysical and structural basis underlying ALK1 signaling. The TGF-β family ligands BMP9 and BMP10 as well as the three type II TGF-β family receptors ActRIIA, ActRIIB, and BMPRII have been implicated in ALK1 signaling. Here, we provide a kinetic and thermodynamic analysis of BMP9 and BMP10 interactions with ALK1 and type II receptors. Our data show that BMP9 displays a significant discrimination in type II receptor binding, whereas BMP10 does not. We also report the crystal structure of a fully assembled ternary complex of BMP9 with the extracellular domains of ALK1 and ActRIIB. The structure reveals that the high specificity of ALK1 for BMP9/10 is determined by a novel orientation of ALK1 with respect to BMP9, which leads to a unique set of receptor-ligand interactions. In addition, the structure explains how BMP9 discriminates between low and high affinity type II receptors. Taken together, our findings provide structural and mechanistic insights into ALK1 signaling that could serve as a basis for novel anti-angiogenic therapies.