Biofilm formation on human immune cells is a multicellular predation strategy of Vibrio cholerae.

Biofilm formation is generally recognized as a bacterial defense mechanism against environmental threats, including antibiotics, bacteriophages, and leukocytes of the human immune system. Here, we show that for the human pathogen Vibrio cholerae, biofilm formation is not only a protective trait but also an aggressive trait to collectively predate different immune cells. We find that V. cholerae forms biofilms on the eukaryotic cell surface using an extracellular matrix comprising primarily mannose-sensitive hemagglutinin pili, toxin-coregulated pili, and the secreted colonization factor TcpF, which differs from the matrix composition of biofilms on other surfaces. These biofilms encase immune cells and establish a high local concentration of a secreted hemolysin to kill the immune cells before the biofilms disperse in a c-di-GMP-dependent manner. Together, these results uncover how bacteria employ biofilm formation as a multicellular strategy to invert the typical relationship between human immune cells as the hunters and bacteria as the hunted.

Single-cell RNA sequencing uncovers the nuclear decoy lincRNA PIRAT as a regulator of systemic monocyte immunity during COVID-19.

The systemic immune response to viral infection is shaped by master transcription factors, such as NF-κB, STAT1, or PU.1. Although long noncoding RNAs (lncRNAs) have been suggested as important regulators of transcription factor activity, their contributions to the systemic immunopathologies observed during SARS-CoV-2 infection have remained unknown. Here, we employed a targeted single-cell RNA sequencing approach to reveal lncRNAs differentially expressed in blood leukocytes during severe COVID-19. Our results uncover the lncRNA PIRAT (PU.1-induced regulator of alarmin transcription) as a major PU.1 feedback-regulator in monocytes, governing the production of the alarmins S100A8/A9, key drivers of COVID-19 pathogenesis. Knockout and transgene expression, combined with chromatin-occupancy profiling, characterized PIRAT as a nuclear decoy RNA, keeping PU.1 from binding to alarmin promoters and promoting its binding to pseudogenes in naïve monocytes. NF-κB-dependent PIRAT down-regulation during COVID-19 consequently releases a transcriptional brake, fueling alarmin production. Alarmin expression is additionally enhanced by the up-regulation of the lncRNA LUCAT1, which promotes NF-κB-dependent gene expression at the expense of targets of the JAK-STAT pathway. Our results suggest a major role of nuclear noncoding RNA networks in systemic antiviral responses to SARS-CoV-2 in humans.

Utility of artificial intelligence-based large language models in ophthalmic care.

PURPOSE: With the introduction of ChatGPT, artificial intelligence (AI)-based large language models (LLMs) are rapidly becoming popular within the scientific community. They use natural language processing to generate human-like responses to queries. However, the application of LLMs and comparison of the abilities among different LLMs with their human counterparts in ophthalmic care remain under-reported. RECENT FINDINGS: Hitherto, studies in eye care have demonstrated the utility of ChatGPT in generating patient information, clinical diagnosis and passing ophthalmology question-based examinations, among others. LLMs' performance (median accuracy, %) is influenced by factors such as the iteration, prompts utilised and the domain. Human expert (86%) demonstrated the highest proficiency in disease diagnosis, while ChatGPT-4 outperformed others in ophthalmology examinations (75.9%), symptom triaging (98%) and providing information and answering questions (84.6%). LLMs exhibited superior performance in general ophthalmology but reduced accuracy in ophthalmic subspecialties. Although AI-based LLMs like ChatGPT are deemed more efficient than their human counterparts, these AIs are constrained by their nonspecific and outdated training, no access to current knowledge, generation of plausible-sounding 'fake' responses or hallucinations, inability to process images, lack of critical literature analysis and ethical and copyright issues. A comprehensive evaluation of recently published studies is crucial to deepen understanding of LLMs and the potential of these AI-based LLMs. SUMMARY: Ophthalmic care professionals should undertake a conservative approach when using AI, as human judgement remains essential for clinical decision-making and monitoring the accuracy of information. This review identified the ophthalmic applications and potential usages which need further exploration. With the advancement of LLMs, setting standards for benchmarking and promoting best practices is crucial. Potential clinical deployment requires the evaluation of these LLMs to move away from artificial settings, delve into clinical trials and determine their usefulness in the real world.

Synthesis of Partially Fluorinated Alkyl Triflates by Electrochemical Fluorination (Simons Process).

A scalable straightforward synthesis of monofluoro- and difluoromethyl triflate CF3 SO2 OCH2 F (MH2F ) and CF3 SO2 OCHF2 (MHF2 ) through electrochemical fluorination (ECF, Simons process) of methyl triflate MH3 in anhydrous hydrogen fluoride at nickel anodes is presented. The ECF method is also feasible for the preparation of the deuterated analogues CF3 SO2 OCD2 F (MD2F ) and CF3 SO2 OCDF2 (MD2F ). Surprisingly, no H/D exchange occurs during ECF of CF3 SO2 OCD3 (MD3 ); this provides further evidence for a NiF3 /NiF4 -mediated ECF mechanism. The ECF of selected partially fluorinated ethyl triflates is described, and electrochemical fluorination of CF3 SO2 OCH2 CF3 (EH2F3 ) leads to the until now unknown chiral CF3 SO2 OCHFCF3 (EHFF3 ). The analogous fluoromethyl and fluoroethyl nonaflates are also accessible by ECF. This study contains detailed spectroscopic, structural, and thermal data on (fluoro)methyl and fluoro(ethyl) triflates.

Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis.

Gram-negative bacteria naturally secrete nano-sized outer membrane vesicles (OMVs), which are important mediators of communication and pathogenesis. OMV uptake by host cells activates TLR signalling via transported PAMPs. As important resident immune cells, alveolar macrophages are located at the air-tissue interface where they comprise the first line of defence against inhaled microorganisms and particles. To date, little is known about the interplay between alveolar macrophages and OMVs from pathogenic bacteria. The immune response to OMVs and underlying mechanisms are still elusive. Here, we investigated the response of primary human macrophages to bacterial vesicles (Legionella pneumophila, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Streptococcus pneumoniae) and observed comparable NF-κB activation across all tested vesicles. In contrast, we describe differential type I IFN signalling with prolonged STAT1 phosphorylation and strong Mx1 induction, blocking influenza A virus replication only for Klebsiella, E.coli and Salmonella OMVs. OMV-induced antiviral effects were less pronounced for endotoxin-free Clear coli OMVs and Polymyxin-treated OMVs. LPS stimulation could not mimic this antiviral status, while TRIF knockout abrogated it. Importantly, supernatant from OMV-treated macrophages induced an antiviral response in alveolar epithelial cells (AEC), suggesting OMV-induced intercellular communication. Finally, results were validated in an ex vivo infection model with primary human lung tissue. In conclusion, Klebsiella, E.coli and Salmonella OMVs induce antiviral immunity in macrophages via TLR4-TRIF-signaling to reduce viral replication in macrophages, AECs and lung tissue. These gram-negative bacteria induce antiviral immunity in the lung through OMVs, with a potential decisive and tremendous impact on bacterial and viral coinfection outcome. Video Abstract.

Effect of peripheral defocus on axial growth and modulation of refractive error in children with anisohyperopia.

PURPOSE: To establish whether axial growth and refractive error can be modulated in anisohyperopic children by imposing relative peripheral hyperopic defocus (RPHD) using multifocal soft contact lenses. METHODS: This study is a prospective, controlled paired-eye study with anisohyperopic children. Axial growth and refractive error were observed without intervention for the first 6 months of the 3-year trial with participants wearing single vision spectacles. Then, participants wore a centre-near, multifocal, soft contact lens (+2.00 D add) in their more hyperopic eye for 2 years, with a single vision contact lens worn in the fellow eye if required. The 'centre-near' portion of the contact lens in the more hyperopic eye corrected distance refractive error while the 'distance' portion imposed hyperopic defocus in the peripheral retina. Participants reverted to single vision spectacles for the final 6 months. RESULTS: Eleven participants, mean age of 10.56 years (SD 1.43; range 8.25-13.42), completed the trial. No increase in axial length (AL) was found during the first 6 months in either eye (p > 0.99). Axial growth across the 2-year intervention period was 0.11 mm (SEM 0.03; p = 0.06) in the test eye versus 0.15 mm (SEM 0.03; p = 0.003) in the control eye. AL was invariant during the final 6 months in both eyes (p > 0.99). Refractive error was stable during the first 6 months in both eyes (p = 0.71). Refractive error change across the 2-year intervention period was -0.23 D (SEM 0.14; p = 0.32) in the test eye versus -0.30 D (SEM 0.14; p = 0.61) in the control eye. Neither eye demonstrated a change in refractive error during the final 6 months (p > 0.99). CONCLUSIONS: Imposing RPHD using the centre-near, multifocal, contact lens specified here did not accelerate axial growth nor reduce refractive error in anisohyperopic children.

Assessing the utility of ChatGPT as an artificial intelligence-based large language model for information to answer questions on myopia.

PURPOSE: ChatGPT is an artificial intelligence language model, which uses natural language processing to simulate human conversation. It has seen a wide range of applications including healthcare education, research and clinical practice. This study evaluated the accuracy of ChatGPT in providing accurate and quality information to answer questions on myopia. METHODS: A series of 11 questions (nine categories of general summary, cause, symptom, onset, prevention, complication, natural history, treatment and prognosis) were generated for this cross-sectional study. Each question was entered five times into fresh ChatGPT sessions (free from influence of prior questions). The responses were evaluated by a five-member team of optometry teaching and research staff. The evaluators individually rated the accuracy and quality of responses on a Likert scale, where a higher score indicated greater quality of information (1: very poor; 2: poor; 3: acceptable; 4: good; 5: very good). Median scores for each question were estimated and compared between evaluators. Agreement between the five evaluators and the reliability statistics of the questions were estimated. RESULTS: Of the 11 questions on myopia, ChatGPT provided good quality information (median scores: 4.0) for 10 questions and acceptable responses (median scores: 3.0) for one question. Out of 275 responses in total, 66 (24%) were rated very good, 134 (49%) were rated good, whereas 60 (22%) were rated acceptable, 10 (3.6%) were rated poor and 5 (1.8%) were rated very poor. Cronbach's α of 0.807 indicated good level of agreement between test items. Evaluators' ratings demonstrated 'slight agreement' (Fleiss's κ, 0.005) with a significant difference in scoring among the evaluators (Kruskal-Wallis test, p < 0.001). CONCLUSION: Overall, ChatGPT generated good quality information to answer questions on myopia. Although ChatGPT shows great potential in rapidly providing information on myopia, the presence of inaccurate responses demonstrates that further evaluation and awareness concerning its limitations are crucial to avoid potential misinterpretation.

Implementation considerations for non-communicable disease-related integration in primary health care: a rapid review of qualitative evidence.

BACKGROUND: Integrated delivery of primary health care (PHC) services is a health reform recommended for achieving ambitious targets of the Sustainable Development Goals and Universal Health Coverage, responding to growing challenges of managing non-communicable and multimorbidity. However, more evidence is needed on effective implementation of PHC integration in different country settings. OBJECTIVE: This rapid review synthesized qualitative evidence on implementation factors affecting integration of non-communicable disease (NCD) into PHC, from the perspective of implementers. The review contributes evidence to inform the World Health Organizations' guidance on integration of NCD control and prevention to strengthen health systems. METHOD: The review was guided by standard methods for conducting rapid systematic reviews. Data analysis was guided by the SURE and WHO health system building blocks frameworks. We used Confidence in the Evidence of Reviews of Qualitative Research (GRADE-CERQual) to assess the confidence of the main findings. RESULTS: The review identified 81 records eligible for inclusion, from 595 records screened. We sampled 20 studies for analysis (including 3 from expert recommendations). Studies covered a wide range of countries (27 countries from 6 continents), the majority from low-and middle-income countries (LMICs), with a diverse set of NCD-related PHC integration combinations and implementation strategies. The main findings were categorised into three overarching themes and several sub-themes. These are, A: Policy alignment and governance, B: Health systems readiness, intervention compatibility and leadership, and C: Human resource management, development, and support. The three overarching findings were assessed as each having a moderate level of confidence. CONCLUSION: The review findings present insights on how health workers responses may be shaped by the complex interaction of individual, social, and organizational factors that may be specific to the context of the intervention, the importance of cross-cutting influences such as policy alignment, supportive leadership and health systems constraints, knowledge that can inform the development of future implementation strategies and implementation research.

Noncoding RNA MaIL1 is an integral component of the TLR4-TRIF pathway.

RNA has been proposed as an important scaffolding factor in the nucleus, aiding protein complex assembly in the dense intracellular milieu. Architectural contributions of RNA to cytosolic signaling pathways, however, remain largely unknown. Here, we devised a multidimensional gradient approach, which systematically locates RNA components within cellular protein networks. Among a subset of noncoding RNAs (ncRNAs) cosedimenting with the ubiquitin-proteasome system, our approach unveiled ncRNA MaIL1 as a critical structural component of the Toll-like receptor 4 (TLR4) immune signal transduction pathway. RNA affinity antisense purification-mass spectrometry (RAP-MS) revealed MaIL1 binding to optineurin (OPTN), a ubiquitin-adapter platforming TBK1 kinase. MaIL1 binding stabilized OPTN, and consequently, loss of MaIL1 blunted OPTN aggregation, TBK1-dependent IRF3 phosphorylation, and type I interferon (IFN) gene transcription downstream of TLR4. MaIL1 expression was elevated in patients with active pulmonary infection and was highly correlated with IFN levels in bronchoalveolar lavage fluid. Our study uncovers MaIL1 as an integral RNA component of the TLR4-TRIF pathway and predicts further RNAs to be required for assembly and progression of cytosolic signaling networks in mammalian cells.

Classification of Skull Shape Deformities Related to Craniosynostosis on 3D Photogrammetry.

Implementation of the Utrecht Cranial Shape Quantificator (UCSQ) classification method on 3D photogrammetry in patients with different types of craniosynostosis is the aim of the present study. Five children (age <1 year) of every group of the common craniosynostoses (scaphocephaly, brachycephaly, trigonocephaly, right-sided and left-sided anterior plagiocephaly) were randomly included. The program 3-Matic (v13.0) was used to import and analyze the included 3dMD photos. Three external landmarks were placed. Using the landmarks, a base plane was created, as well as a plane 4 cm superior to the base plane. Using UCSQ, we created sinusoid curves of the patients, the resulting curves were analyzed and values were extracted for calculations. Results per patient were run through a diagnostic flowchart in order to determine correctness of the flowchart when using 3D photogrammetry. Each of the patients (n=25) of the different craniosynostosis subgroups is diagnosed correctly based on the different steps in the flowchart. This study proposes and implements a diagnostic approach of craniosynostosis based on 3D photogrammetry. By using a diagnostic flowchart based on specific characteristics for every type of craniosynostosis related to specific skull deformities, diagnosis can be established. All variables are expressed in number and are therefore objective.

Pharmacohistory of Cannabis Use-A New Possibility in Future Drug Development for Gastrointestinal Diseases.

Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, and leaves have been utilized to alleviate pain, inflammation, anxiety, and gastrointestinal disorders like nausea, vomiting, diarrhoea, and inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures and religions. Despite multi-dimensional uses, the global prohibition of cannabis by the USA through the introduction of the Marijuana Tax Act in 1937 led to prejudice about the perceived risks of cannabis, overshadowing its medicinal potential. Nevertheless, the discovery of tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, and the endocannabinoid system renewed scientific interest in understanding the role of cannabis in modulating different conditions, including gastrointestinal disorders. Preparations combining cannabidiol and THC have shown promise in mitigating gut symptoms through anti-inflammatory and motility-enhancing effects. This review revisits the ethnomedicinal use of cannabis in gastrointestinal diseases and emphasizes the need for further research to determine optimal dosages, formulations, and safety profiles of cannabis-based medicines. It also underscores the future potential of cannabinoid-based therapies by leveraging the role of the expanded endocannabinoid system, an endocannabinoidome, in the modulation of gastrointestinal ailments.

UCSQ Method Applied on 3D Photogrammetry: Non-Invasive Objective Differentiation Between Synostotic and Positional Plagiocephaly.

OBJECTIVE: Objective differentiation between unilateral coronal synostosis (UCS) and positional posterior plagiocephaly (PPP) based on 3D photogrammetry according to Utrecht Cranial Shape Quantificator (UCSQ). DESIGN: Retrospective study. SETTING: Primary craniofacial center. PATIENTS, PARTICIPANTS: Thirty-two unoperated patients (17 UCS; 15 PPP) (age < 1 year). INTERVENTIONS: Extraction of variables from sinusoid curves derived using UCSQ: asymmetry ratio forehead and occiput peak, ratio of gradient forehead and occiput peak, location forehead and occiput peak. MAIN OUTCOME MEASURE(S): Variables, derived using 3D photogrammetry, were analyzed for differentiation between UCS and PPP. RESULTS: Frontal peak was shifted to the right side of the head in left-sided UCS (mean x-value 207 [192-220]), and right-sided PPP (mean x-value 210 [200-216]), and to the left in right-sided UCS (mean x-value 161 [156-166]), and left-sided PPP (mean x-value 150 [144-154]). Occipital peak was significantly shifted to the right side of the head in left-sided PPP (mean x-value 338 [336-340]) and to the left in right-sided PPP (mean x-value 23 [14-32]). Mean x-value of occipital peak was 9 (354-30) in left- and 2 (350-12) in right-sided UCS. Calculated ratio of gradient of the frontal peak is, in combination with the calculated asymmetry ratio of the frontal peak, a distinctive finding. CONCLUSIONS: UCSQ objectively captures shape of synostotic and positional plagiocephaly using 3D photogrammetry, we therefore developed a suitable method to objectively differentiate UCS from PPP using radiation-free methods.

Dual RNA-seq unveils noncoding RNA functions in host-pathogen interactions.

Bacteria express many small RNAs for which the regulatory roles in pathogenesis have remained poorly understood due to a paucity of robust phenotypes in standard virulence assays. Here we use a generic 'dual RNA-seq' approach to profile RNA expression simultaneously in pathogen and host during Salmonella enterica serovar Typhimurium infection and reveal the molecular impact of bacterial riboregulators. We identify a PhoP-activated small RNA, PinT, which upon bacterial internalization temporally controls the expression of both invasion-associated effectors and virulence genes required for intracellular survival. This riboregulatory activity causes pervasive changes in coding and noncoding transcripts of the host. Interspecies correlation analysis links PinT to host cell JAK-STAT signalling, and we identify infection-specific alterations in multiple long noncoding RNAs. Our study provides a paradigm for a sensitive RNA-based analysis of intracellular bacterial pathogens and their hosts without physical separation, as well as a new discovery route for hidden functions of pathogen genes.

A ribosomal RNA fragment with 2',3'-cyclic phosphate and GTP-binding activity acts as RIG-I ligand.

The RNA helicase RIG-I plays a key role in sensing pathogen-derived RNA. Double-stranded RNA structures bearing 5'-tri- or diphosphates are commonly referred to as activating RIG-I ligands. However, endogenous RNA fragments generated during viral infection via RNase L also activate RIG-I. Of note, RNase-digested RNA fragments bear a 5'-hydroxyl group and a 2',3'-cyclic phosphate. How endogenous RNA fragments activate RIG-I despite the lack of 5'-phosphorylation has not been elucidated. Here we describe an endogenous RIG-I ligand (eRL) that is derived from the internal transcribed spacer 2 region (ITS2) of the 45S ribosomal RNA after partial RNase A digestion in vitro, RNase A protein transfection or RNase L activation. The immunostimulatory property of the eRL is dependent on 2',3'-cyclic phosphate and its sequence is characterized by a G-quadruplex containing sequence motif mediating guanosine-5'-triphosphate (GTP) binding. In summary, RNase generated self-RNA fragments with 2',3'-cyclic phosphate function as nucleotide-5'-triphosphate binding aptamers activating RIG-I.

The effect of peripheral defocus on axial growth and modulation of refractive error in hyperopes.

PURPOSE: To establish whether axial growth and refractive error can be modulated in hyperopic children by imposing relative peripheral hyperopic defocus using multifocal soft contact lenses. METHODS: A prospective controlled study with hyperopic participants allocated to a control or test group. Control group participants were corrected with single vision spectacles and changes to axial length and refractive error were followed for 3 years. For the test group, axial growth and post-cycloplegic refractive error were observed with participants wearing single vision spectacles for the first 6 months of the trial and then corrected with centre-near multifocal soft contact lenses with a 2.00 D add for 2 years. The central 'near' portion of the contact lens corrected distance refractive error while the 'distance' portion imposed hyperopic defocus. Participants reverted to single vision spectacles for the final 6 months of the study. RESULTS: Twenty-two participants, mean age 11.13 years (SD 1.72) (range 8.33-13.92), completed the trial. Axial length did not change during the first 6 months in either group (p = 1.00). Axial growth across the 2-year intervention period was 0.17 mm (SEM 0.04) (p < 0.0005) in the test group versus 0.06 mm (SEM 0.07) (p = 0.68) in the control group. Axial length was invariant during the final 6 months in either group (p = 1.00). Refractive error was stable during the first 6 months in both groups (p = 1.00). Refractive error change across the 2-year intervention period was -0.26 D (SEM 0.14) (p = 0.38) in the test group versus -0.01 D (SEM 0.09) (p = 1.00) in the control group. Neither the test (p = 1.00) nor control (p = 0.63) group demonstrated a change in refractive error during the final 6 months. CONCLUSIONS: The rate of axial growth can be accelerated in children with hyperopia using centre-near multifocal soft contact lenses.

X-ray induced photodynamic therapy with copper-cysteamine nanoparticles in mice tumors.

Photodynamic therapy (PDT), a treatment that uses a photosensitizer, molecular oxygen, and light to kill target cells, is a promising cancer treatment method. However, a limitation of PDT is its dependence on light that is not highly penetrating, precluding the treatment of tumors located deep in the body. Copper-cysteamine nanoparticles are a new type of photosensitizer that can generate cytotoxic singlet oxygen molecules upon activation by X-rays. In this paper, we report on the use of copper-cysteamine nanoparticles, designed to be targeted to tumors, for X-ray-induced PDT. In an in vivo study, results show a statistically significant reduction in tumor size under X-ray activation of pH-low insertion peptide-conjugated, copper-cysteamine nanoparticles in mouse tumors. This work confirms the effectiveness of copper-cysteamine nanoparticles as a photosensitizer when activated by radiation and suggests that these Cu-Cy nanoparticles may be good candidates for PDT in deeply seated tumors when combined with X-rays and conjugated to a tumor-targeting molecule.

Intracranial Volume Not Correlated With Severity in Trigonocephaly.

OBJECTIVES: Severity of trigonocephaly varies and potentially affects intracranial volume (ICV) and intracranial pressure (ICP). The aim of this study is to measure ICV in trigonocephaly patients and compare it to normative data and correlate ICV with the severity of the skull deformity according to UCSQ (Utrecht Cranial Shape Quantifier). DESIGN: Retrospective study. SETTING: Primary craniofacial center. PATIENTS, PARTICIPANTS: Nineteen preoperative patients with nonsyndromic trigonocephaly (age ≤12 months). INTERVENTION: Intracranial volume was measured on preoperative computed tomography (CT) scans by manual segmentation (OsiriX Fondation). Utrecht Cranial Shape Quantifier was used to quantify the severity of the skull deformity. When present, papilledema as sign of elevated ICP was noted. MAIN OUTCOME MEASURES(S): Measured ICV was compared to Lichtenberg normative cranial volume growth curves, and Pearson correlation coefficient was used to correlate UCSQ with the ICV. RESULTS: Mean age at CT scan was 6 months (2-11). Mean measured ICV was 842 mL (579-1124). Thirteen of h19 patients (11/15 boys and 2/4 girls) had an ICV between ±2 SD curves of Lichtenberg, 2 of 19 (1/15 boys and 1/4 girls) had an ICV less than -2 SD and 4 of 19 (3/15 boys and 1/4 girls) had an ICV greater than +2 SD. Mean UCSQ severity of trigonocephaly was 2.40 (-622.65 to 1279.75). Correlation between severity and ICV was negligible (r = -0.11). No papilledema was reported. CONCLUSIONS: Measured ICV was within normal ranges for trigonocephaly patients, in both mild and severe cases. No correlation was found between severity of trigonocephaly and ICV.

Validation of Skully Care as a Fast Method for Quantifying Positional Cranial Deformities.

OBJECTIVE: Craniofacial measuring is valuable for diagnosis and evaluation of growth and treatment of positional skull deformities. Plagiocephalometry (PCM) quantifies skull deformities and is proven to be reliable and valid. However, PCM needs direct skin contact with thermoplastic material, is laborious and time-consuming. Therefore, Skully Care (SC) was developed to measure positional skull deformities with a smartphone application. DESIGN: SC is retrospectively compared to PCM. SETTING: Pediatric physiotherapy centers. PATIENTS: Age ≤1 year, analyzed or treated for positional skull deformities. INTERVENTIONS: A total of 60 skull shape analyses were performed. MAIN OUTCOME MEASURES: The main outcome measures employed are Pearson correlation coefficient between cranial vault asymmetry index (CVAI; in SC) and oblique diameter difference index (ODDI; in PCM) and between cranial index (CI; in SC) and cranial proportional index (CPI; in PCM). Mann-Whitney U test determined difference of time consumption between PCM and SC. RESULTS: High correlation was found between CVAI and ODDI (r = 0.849; P < .01) in positional plagiocephaly and very high correlation between CI and CPI (r = 0.938; P < .01) in positional brachycephaly. SC is significantly faster than PCM (P < .001). CONCLUSIONS: SC is valid in analyzing positional skull deformities and strongly correlates to PCM, the gold standard in daily physiotherapy practice. The combination of simplicity, validity, speed, and user and child convenience makes SC a promising craniofacial measuring method in daily practice. SC has potential to be the modern successor for analyzing positional skull deformities.

Stable and Storable N(CF3 )2 Transfer Reagents.

Fluorinated groups are essential for drug design, agrochemicals, and materials science. The bis(trifluoromethyl)amino group is an example of a stable group that has a high potential. While the number of molecules containing perfluoroalkyl, perfluoroalkoxy, and other fluorinated groups is steadily increasing, examples with the N(CF3 )2 group are rare. One reason is that transfer reagents are scarce and metal-based storable reagents are unknown. Herein, a set of CuI and AgI bis(trifluoromethyl)amido complexes stabilized by N- and P-donor ligands with unprecedented stability are presented. The complexes are stable solids that can even be manipulated in air for a short time. They are bis(trifluoromethyl)amination reagents as shown by nucleophilic substitution and Sandmeyer reactions. In addition to a series of benzylbis(trifluoromethyl)amines, 2-bis(trifluoromethyl)amino acetate was obtained, which, upon hydrolysis, gives the fluorinated amino acid N,N-bis(trifluoromethyl)glycine.

Influenza virus-mediated suppression of bronchial Chitinase-3-like 1 secretion promotes secondary pneumococcal infection.

Infections of the lung are among the leading causes of death worldwide. Despite the preactivation of innate defense programs during viral infection, secondary bacterial infection substantially elevates morbidity and mortality rates. Particularly problematic are co-infections with influenza A virus (IAV) and the major bacterial pathogen Streptococcus pneumoniae. However, the molecular processes underlying the severe course of such co-infections are not fully understood. Previously, the absence of secreted glycoprotein Chitinase-3-like 1 (CHI3L1) was shown to increase pneumococcal replication in mice. We therefore hypothesized that an IAV preinfection decreases CHI3L1 levels to promote pneumococcal infection. Indeed, in an air-liquid interface model of primary human bronchial epithelial cells (hBECs), IAV preinfection interfered with apical but not basolateral CHI3L1 release. Confocal time-lapse microscopy revealed that the gradual loss of apical CHI3L1 localization during co-infection with influenza and S. pneumoniae coincided with the disappearance of goblet as well as ciliated cells and increased S. pneumoniae replication. Importantly, extracellular restoration of CHI3L1 levels using recombinant protein significantly reduced bacterial load in influenza preinfected bronchial models. Thus, recombinant CHI3L1 may provide a novel therapeutic means to lower morbidity and mortality associated with post-influenza pneumococcal infections.