Chiroptical Strain Sensors from Electrospun Cadmium Sulfide Quantum-Dot Fibers.

Controllable synthesis of homochiral nano/micromaterials has been a constant challenge for fabricating various stimuli-responsive chiral sensors. To provide an avenue to this goal, we report electrospinning as a simple and economical strategy to form continuous homochiral microfibers with strain-sensitive chiroptical properties. First, electrospun homochiral microfibers from self-assembled cadmium sulfide (CdS) quantum dot magic-sized clusters (MSCs) are produced. Highly sensitive and reversible strain sensors are then fabricated by embedding these chiroptically active fibers into elastomeric films. The chiroptical response on stretching is indicated quantitatively as reversible changes in magnitude, spectral position (wavelength), and sign in circular dichroism (CD) and linear dichroism (LD) signals and qualitatively as a prominent change in the birefringence features under cross-polarizers. The observed periodic twisted helical fibrils at the surface of fibers provide insights into the origin of the fibers' chirality. The measurable shifts in CD and LD are caused by elastic deformations of these helical fibrillar structures of the fiber. To elucidate the origin of these chiroptical properties, we used field emission-electron microscopy (FE-SEM), atomic force microscopy (AFM), synchrotron X-ray analysis, polarized optical microscopy, as well as measurements to isolate the true CD, and contributions from photoelastic modulators (PEM) and LD. Our findings thus offer a promising strategy to fabricate chiroptical strain-sensing devices with multiple measurables/observables using electric-field-assisted spinning of homochiral nano/microfibers.

Gasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation.

Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of the inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation of GSDMD in knockout (KO) mice (Gsdmd-/-) significantly attenuates influenza virus-induced weight loss, lung dysfunction, lung histopathology, and mortality compared with wild type (WT) mice, despite similar viral loads. Infected Gsdmd-/- mice exhibit decreased inflammatory gene signatures shown by lung transcriptomics. Among these, diminished neutrophil gene activation signatures are corroborated by decreased detection of neutrophil elastase and myeloperoxidase in KO mouse lungs. Indeed, directly infected neutrophils are observed in vivo and infection of neutrophils in vitro induces release of DNA and tissue-damaging enzymes that is largely dependent on GSDMD. Neutrophil depletion in infected WT mice recapitulates the reductions in mortality, lung inflammation, and lung dysfunction observed in Gsdmd-/- animals, while depletion does not have additive protective effects in Gsdmd-/- mice. These findings implicate a function for GSDMD in promoting lung neutrophil responses that amplify influenza virus-induced inflammation and pathogenesis. Targeting the GSDMD/neutrophil axis may provide a therapeutic avenue for treating severe influenza.

Classification of formalin-fixed bladder cancer cells with laser tweezer Raman spectroscopy.

Bladder cancer is a common cancer that is relatively hard to detect at an early stage because of its non-obvious symptoms. It is known that bladder cells can be found in urine samples which potentially could be used for early detection of bladder cancer. Raman spectroscopy is a powerful non-invasive tool for accessing biochemical information of cells. Combined with laser tweezers, to allow isolation of single cells, Raman spectroscopy has been used to characterise a number of bladder cells that might be found in a urine sample. Using principal component-canonical variates analysis (PC-CVA) and k-fold validation, the results shows that the invasive bladder cancer cells can be identified with accuracy greater than 87%. This demonstrates the potential of developing an early detection method that identifies the invasive bladder cancer cells in urine samples.

Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rß2.

IL-35 is an immunosuppressive cytokine with roles in cancer, autoimmunity, and infectious disease. In the conventional model of IL-35 biology, the p35 and Ebi3 domains of this cytokine interact with IL-12Rß2 and gp130, respectively, on the cell surface of regulatory T and regulatory B cells, triggering their suppression of Th cell activity. Here we use a human IL-12 bioactivity reporter cell line, protein binding assays, and primary human Th cells to demonstrate an additional mechanism by which IL-35 suppresses Th cell activity, wherein IL-35 directly inhibits the association of IL-12 with its surface receptor IL-12Rß2 and downstream IL-12-dependent activities. IL-12 binding to the surface receptor IL-12Rß1 was unaffected by IL-35. These data demonstrate that in addition to acting via regulatory T and regulatory B cells, human IL-35 can also directly suppress IL-12 bioactivity and its interaction with IL-12Rß2.

UV222 disinfection of SARS-CoV-2 in solution.

There is an urgent need for evidence-based engineering controls to reduce transmission of SARS-CoV-2, which causes COVID-19. Although ultraviolet (UV) light is known to inactivate coronaviruses, conventional UV lamps contain toxic mercury and emit wavelengths (254 nm) that are more hazardous to humans than krypton chlorine excimer lamps emitting 222 nm (UV222). Here we used culture and molecular assays to provide the first dose response for SARS-CoV-2 solution exposed to UV222. Culture assays (plaque infectivity to Vero host) demonstrated more than 99.99% disinfection of SARS-CoV-2 after a UV222 dose of 8 mJ/cm2 (pseudo-first order rate constant = 0.64 cm2/mJ). Immediately after UV222 treatment, RT-qPCR assays targeting the nucleocapsid (N) gene demonstrated ~ 10% contribution of N gene damage to disinfection kinetics, and an ELISA assay targeting the N protein demonstrated no contribution of N protein damage to disinfection kinetics. Molecular results suggest other gene and protein damage contributed more to disinfection. After 3 days incubation with host cells, RT-qPCR and ELISA kinetics of UV222 treated SARS-CoV-2 were similar to culture kinetics, suggesting validity of using molecular assays to measure UV disinfection without culture. These data provide quantitative disinfection kinetics which can inform implementation of UV222 for preventing transmission of COVID-19.

Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection.

Nontuberculous mycobacteria (NTM) are an increasingly common cause of respiratory infection in people with cystic fibrosis (PwCF). Relative to those with no history of NTM infection (CF-NTMNEG), PwCF and a history of NTM infection (CF-NTMPOS) are more likely to develop severe lung disease and experience complications over the course of treatment. In other mycobacterial infections (e.g., tuberculosis), an overexuberant immune response causes pathology and compromises organ function; however, since the immune profiles of CF-NTMPOS and CF-NTMNEG airways are largely unexplored, it is unknown which, if any, immune responses distinguish these cohorts or concentrate in damaged tissues. Here, we evaluated lung lobe-specific immune profiles of 3 cohorts (CF-NTMPOS, CF-NTMNEG, and non-CF adults) and found that CF-NTMPOS airways are distinguished by a hyperinflammatory cytokine profile. Importantly, the CF-NTMPOS airway immune profile was dominated by B cells, classical macrophages, and the cytokines that support their accumulation. These and other immunological differences between cohorts, including the near absence of NK cells and complement pathway members, were enriched in the most damaged lung lobes. The implications of these findings for our understanding of lung disease in PwCF are discussed, as are how they may inform the development of host-directed therapies to improve NTM disease treatment.

Pulmonary and Critical Care Considerations for e-Cigarette, or Vaping, Product Use-Associated Lung Injury.

BACKGROUND: In 2019, the United States experienced a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). More than one-half of these patients required admission to an ICU. RESEARCH QUESTION: What are the recent literature and expert opinions which inform the diagnosis and management of patients with critical illness with EVALI? STUDY DESIGN AND METHODS: To synthesize information critical to pulmonary/critical care specialists in the care of patients with EVALI, this study examined data available from patients hospitalized with EVALI between August 2019 and January 2020; reviewed the clinical course and critical care experience with those patients admitted to the ICU; and compiled opinion of national experts. RESULTS: Of the 2,708 patients with confirmed or probable EVALI requiring hospitalization as of January 21, 2020, a total of 1,604 (59.2%) had data available on ICU admission; of these, 705 (44.0%) were admitted to the ICU and are included in this analysis. The majority of ICU patients required respiratory support (88.5%) and in severe cases required intubation (36.1%) or extracorporeal membrane oxygenation (6.7%). The majority (93.0%) of these ICU patients survived to discharge. Review of the clinical course and expert opinion provided insight into: imaging; considerations for bronchoscopy; medical treatment, including use of empiric antibiotics, antiviral agents, and corticosteroids; respiratory support, including considerations for intubation, positioning maneuvers, and extracorporeal membrane oxygenation; and patient outcomes. INTERPRETATION: Review of the clinical course of patients with EVALI requiring ICU admission and compilation of expert opinion provided critical insight into pulmonary/critical care-specific considerations for this patient population. Because a large proportion of patients hospitalized with EVALI required ICU admission, it is important to remain prepared to care for patients with EVALI.

Enhanced Li-ion diffusion and electrochemical performance in strained-manganese-iron oxide core-shell nanoparticles.

Efforts to improve energy storage depend greatly on the development of efficient electrode materials. Recently, strain has been employed as an alternate approach to improve ion mobility. While lattice strain has been well-researched in catalytic applications, its effects on electrochemical energy storage are largely limited to computational studies due to complexities associated with strain control in nanomaterials as well as loss of strain due to the phase change of the active material during charging-discharging. In this work, we overcome these challenges and investigate the effects of strain on supercapacitor performance in Li-ion-based energy devices. We synthesize epitaxial Fe3O4@MnFe2O4 (core@shell) nanoparticles with varying shell thickness to control the lattice strain. A narrow voltage window for electrochemical testing is used to limit the storage mechanism to lithiation-delithiation, preventing a phase change and maintaining structural strain. Cyclic voltammetry reveals a pseudocapacitive behavior and similar levels of surface charge storage in both strained- and unstrained-MnFe2O4 samples; however, diffusive charge storage in the strained sample is twice as high as the unstrained sample. The strained-MnFe2O4 electrode exceeds the performance of the unstrained-MnFe2O4 electrode in energy density by ∼33%, power density by ∼28%, and specific capacitance by ∼48%. Density functional theory shows lower formation energies for Li-intercalation and lower activation barrier for Li-diffusion in strained-MnFe2O4, corresponding to a threefold increase in the diffusion coefficient. The enhanced Li-ion diffusion rate in the strained-electrodes is further confirmed using the galvanostatic intermittent titration technique. This work provides a starting point to using strain engineering as a novel approach for designing high performance energy storage devices.

Discovery of Icenticaftor (QBW251), a Cystic Fibrosis Transmembrane Conductance Regulator Potentiator with Clinical Efficacy in Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel are established as the primary causative factor in the devastating lung disease cystic fibrosis (CF). More recently, cigarette smoke exposure has been shown to be associated with dysfunctional airway epithelial ion transport, suggesting a role for CFTR in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, the identification and characterization of a high throughput screening hit 6 as a potentiator of mutant human F508del and wild-type CFTR channels is reported. The design, synthesis, and biological evaluation of compounds 7-33 to establish structure-activity relationships of the scaffold are described, leading to the identification of clinical development compound icenticaftor (QBW251) 33, which has subsequently progressed to deliver two positive clinical proofs of concept in patients with CF and COPD and is now being further developed as a novel therapeutic approach for COPD patients.

Vaping Associated Pulmonary Nontuberculous Mycobacteria.

INTRODUCTION: E-cigarette or vaping product use associated lung injury (EVALI) has been an important health risk in both children and adults. The pathophysiology of EVALI is not well understood. However, it is speculated that certain substances such as Vitamin E Acetate (VEA), particularly in marijuana containing vape cartridges may result in lung injury and lead to respiratory dysfunction. EVALI is often seen in the absence of infections, but it has been found to be associated with both fungal and bacterial infections. Like EVALI, nontuberculous mycobacteria (NTM) pulmonary disease is also on the rise, but is primarily reported in immunocompromised individuals. Here, we present three immunocompetent individuals wherein pulmonary NTM infection co-occurred with vaping. METHODS: Medical information including patient history, laboratory, and radiograph reports were abstracted from electronic medical records from participating institutions located in the Bronx, NY, Philadelphia, PA, and Lexington, KY. RESULTS: All three cases were otherwise immunocompetent individuals with a significant history of vaping either nicotine and/or marijuana containing products. The pathogens isolated include Mycobacterium avium complex, M. xenopi, and M. gordonae. All three patients were treated for NTM. CONCLUSION: There is little reported on the association between vaping and NTM. It is possible that vaping may have rendered these individuals to be more susceptible to NTM colonization and infection. The possible mechanisms of vaping lung injury and pulmonary NTM are discussed.

Opposing activities of IFITM proteins in SARS-CoV-2 infection.

Interferon-induced transmembrane proteins (IFITMs) restrict infections by many viruses, but a subset of IFITMs enhance infections by specific coronaviruses through currently unknown mechanisms. We show that SARS-CoV-2 Spike-pseudotyped virus and genuine SARS-CoV-2 infections are generally restricted by human and mouse IFITM1, IFITM2, and IFITM3, using gain- and loss-of-function approaches. Mechanistically, SARS-CoV-2 restriction occurred independently of IFITM3 S-palmitoylation, indicating a restrictive capacity distinct from reported inhibition of other viruses. In contrast, the IFITM3 amphipathic helix and its amphipathic properties were required for virus restriction. Mutation of residues within the IFITM3 endocytosis-promoting YxxФ motif converted human IFITM3 into an enhancer of SARS-CoV-2 infection, and cell-to-cell fusion assays confirmed the ability of endocytic mutants to enhance Spike-mediated fusion with the plasma membrane. Overexpression of TMPRSS2, which increases plasma membrane fusion versus endosome fusion of SARS-CoV-2, attenuated IFITM3 restriction and converted amphipathic helix mutants into infection enhancers. In sum, we uncover new pro- and anti-viral mechanisms of IFITM3, with clear distinctions drawn between enhancement of viral infection at the plasma membrane and amphipathicity-based mechanisms used for endosomal SARS-CoV-2 restriction.

Experiences of using vedolizumab in the treatment of inflammatory bowel disease in the East Midlands UK - a retrospective observational study.

PURPOSE: Clinical trials have demonstrated efficacy of vedolizumab in ulcerative colitis (UC) and Crohn's disease (CD). Further real-world data is needed to inform clinical practice. The primary outcome was to assess corticosteroid-free and clinical remission after vedolizumab initiation. Secondary outcomes included effect on disease activity scores, biochemical markers, concomitant drug use, endoscopic remission, surgical intervention, hospital admissions and adverse events. MATERIALS AND METHODS: A multi-centre retrospective observational study was conducted with patients initiated on vedolizumab across seven UK hospitals 1/11/14-30/11/16. Clinical disease activity was assessed using the partial Mayo Scores (pMS) and Harvey Bradshaw Index (HBI). Clinical remission was defined as HBI ≤4 or pMS <2 with a combined stool frequency and rectal bleeding sub score of ≤1. Clinical response was defined as ≥2-point decrease from baseline in pMS and ≥3-point decrease from baseline in HBI. RESULTS: One hundred ninety-two patients were included in the final analysis. 45% of UC and 10% of CD patients were anti-TNF naive. Over the observation period corticosteroid-free remission rates for UC and CD were 46% and 45%, while clinical remission rates were 52% and 44%, respectively. Time to corticosteroid free remission for UC and CD was 17.6 [IQR: 8.7-29.6] and 14.1 [QR: 6.0-21.7] weeks, respectively. Time to clinical response for UC was 9.4 [IQR: 5.7-15.4] and CD was 9.5 [IQR: 6.1-18.2] weeks. There was a substantial decrease in the concomitant use of immunomodulators and a similar decrease in concomitant corticosteroid use over the study period. CONCLUSIONS: Results in this predominately anti-TNF experienced population mirror other published real-world data, demonstrating good clinical effectiveness and a comparable safety profile.

Diagnóstico y tratamiento de la retinopatía diabética y edema macular diabético: guía de práctica clínica del Seguro Social de Salud del Perú (EsSalud) / Diagnosis and treatment of diabetic retinopathy and diabetic macular edema: clinical practice guidelines of the Peruvian Health Social Security (EsSalud)

RESUMEN Introducción. El presente artículo resume la guía de práctica clínica (GPC) para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en el Seguro Social de Salud del Perú (EsSalud). Objetivo. Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud. Métodos. Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 4 preguntas clínicas a ser respondidas por la presente GPC. Para cada una de estas preguntas se realizó búsquedas de revisiones sistemáticas y de estudios primarios (cuando se consideró pertinente) en PubMed durante el 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buena práctica clínica y el flujograma de manejo. Resultados. La presente GPC abordó 4 preguntas clínicas sobre el tamizaje, diagnóstico, tratamiento de elección y tratamiento adyuvante. En base a estas preguntas se formularon 6 recomendaciones (4 fuertes y 2 condicionales), 19 puntos de buena práctica clínica y 1 flujograma de manejo. Conclusión. El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud.

ABSTRACT Introduction. This article summarizes the clinical practice guidelines (CPG) for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema of the Health Social Security of Peru (EsSalud). Objective. To provide clinical recommendations based on evidence for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema in EsSalud. Methods. A guidelines elaborating group (GEG) was conformed by medical specialists and methodologists. The GEG formulated 4 clinical questions intended to be answered by this CPG. For each of these questions systematic searches of systematic reviews and primary studies (when considered pertinent) were carried out in PubMed during 2018. Evidence was selected in order to reply each of the proposed clinical questions. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. During periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate the recommendations, points of good clinical practice and the management flowchart. Results. The present CPG addressed 4 clinical questions of four topics: screening, diagnosis, treatment of choice and adjuvant treatment. Based on these questions, 6 recommendations (4 strong and 2 conditional), 19 points of good clinical practice, and 1 management flowchart were formulated. Conclusion. This article summarizes the methodology and conclusions based on evidence from the CPG for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema in EsSalud.

Lung T-Cell Profile Alterations are Associated with Bronchiolitis Obliterans Syndrome in Cystic Fibrosis Lung Transplant Recipients.

The contribution of T-cells after lung transplant (LTx) remains controversial with no current consensus of their role concerning chronic lung allograft dysfunction. Using flow cytometry to assess T-cell subsets of bronchoalveolar lavage fluid (BALF) in 16 cystic fibrosis (CF) LTx recipients, we identified a decline in CD4+ T-cell frequency and an increase in CD8+ T-cell frequency in patients who developed severe bronchiolitis obliterans syndrome (BOS) (N = 10) when comparing baseline (6 months post-LTx) and follow-up (most recent bronchoscopy-clinical or surveillance per protocol). Comparing BOS to No BOS cohorts, significant differences were found in CD4+ T-cell frequency [17.4 (12.5, 28.2) vs 46.6 (44.4, 48.4), p = 0.003] and CD8+ T-cell frequency [65.6 (62.8, 75.3) vs 39.2 (32.2, 43.3), p = 0.014], respectively. The mean difference of the CD4:CD8 ratio was 0.87 units lower (95% CI - 1.44 to - 0.30, p = 0.006) than patients without BOS, while the median difference of the CD4:CD8 ratio was 0.92 units lower (95% CI - 1.83 to - 0.009, p = 0.048). Therefore, our results suggest that T-cell profiles measured through flow cytometry of BALF in the CF LTx population are associated with the development of severe BOS. Further work is needed in larger patient populations to validate our findings and to determine if this is useful for recipients who underwent LTx for other indications.

γ-herpesvirus latency attenuates Mycobacterium tuberculosis infection in mice.

Tuberculosis is caused by Mycobacterium tuberculosis (Mtb), a bacterial pathogen which is transmitted via aerosol and establishes a chronic lung infection. In naïve hosts, Mtb grows for several weeks without being restricted by IFNγ-producing T cells, which eventually accumulate and limit Mtb dissemination. In this study, we used a mouse model of Mtb/γ-herpesvirus (γHV) coinfection to test the hypothesis that latent γHV infection alters host resistance to Mtb. γHVs are DNA viruses which elicit a polyclonal T cell response and attenuate some acute bacterial pathogens in mice; whether γHVs modulate infection with Mtb is unknown. Here, mice harboring latent mouse gammaherpesvirus 68 (MHV68)-a γHV genetically and biologically related to human Epstein Barr virus (EBV)-were infected via aerosol with a low dose of virulent Mtb. Mtb burdens and IFNγ+ T cell frequencies in mice with latent MHV68 (MHV68POS mice) were subsequently measured and compared to control mice that did not harbor latent MHV68 (MHV68NEG mice). Relative to MHV68NEG controls, MHV68POS mice more effectively limited Mtb growth and dissemination, and had higher frequencies of CD4+IFNγ+ cells in lung-draining lymph nodes. Collectively, our results support a model wherein latent γHV confers moderate protection against subsequent Mtb infection.

Surveillance for variant CJD: should more children with neurodegenerative diseases have autopsies?

OBJECTIVES: To report investigations performed in children with progressive neurodegenerative diseases reported to this UK study. DESIGN: Since 1997 paediatric surveillance for variant Creutzfeldt-Jakob disease (vCJD) has been performed by identifying children aged less than 16 years with progressive intellectual and neurological deterioration (PIND) and searching for vCJD among them. SETTING: The PIND Study obtains case details from paediatricians who notify via the British Paediatric Surveillance Unit. PARTICIPANTS: Between May 1997 and October 2017, a total of 2050 cases meeting PIND criteria had been notified and investigated. RESULTS: Six children had vCJD. 1819 children had other diagnoses, made in 12 cases by antemortem brain biopsy and in 15 by postmortem investigations. 225 children were undiagnosed: only 3 had antemortem brain biopsies and only 14 of the 108 who died were known to have had autopsies; postmortem neuropathological studies were carried out in just 10% (11/108) and only two had prion protein staining of brain tissue. Of the undiagnosed cases 43% were known to come from Asian British families. CONCLUSIONS: Most of the notified children had a diagnosis other than vCJD to explain their neurological deterioration. None of the undiagnosed cases had the clinical phenotype of vCJD but brain tissue was rarely studied to exclude vCJD. Clinical surveillance via the PIND Study remains the only practical means of searching for vCJD in UK children.

Risks and Benefits of Adjuvant Radiotherapy After Inguinal Lymphadenectomy in Node-positive Penile Cancer: A Systematic Review by the European Association of Urology Penile Cancer Guidelines Panel.

CONTEXT: Management of men with penile squamous cell carcinoma (PSCC) who have high-risk features following radical inguinal lymphadenectomy (ILND) remains controversial. European Association of Urology guidelines state that adjuvant inguinal radiotherapy (AIRT) is "not generally recommended". Despite this, many centres continue to offer AIRT to a subset of men. OBJECTIVE: To undertake a systematic review of the evidence on AIRT in node-positive men with PSCC. EVIDENCE ACQUISITION: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with no language or date restriction. Inclusion criteria were men with PSCC, pathologically staged inguinal node positive after ILND. The intervention included ILND with AIRT compared with ILND alone. Primary outcomes were relapse-free survival and toxicity. Risk of bias assessment was undertaken. EVIDENCE SYNTHESIS: A total of 913 abstracts were identified and screened independently by two reviewers. Seven studies were eligible for inclusion: six full-text manuscripts and one conference abstract. All were retrospective series and at a high risk of bias. The selected studies included 1605 men. Indications for AIRT varied but were typically involvement of two or more inguinal nodes or extranodal extension. Regional recurrence rate following AIRT was reported at 10-91.7%. Only one study reported on toxicity. Two studies compared recurrence and survival between men who received and who did not receive AIRT, with no significant difference (p>0.05). CONCLUSIONS: The evidence indicates that men treated with AIRT do not gain benefit with respect to relapse or survival. Uncertainty remains due to the retrospective nature and high risks of bias across the evidence. Given the lack of evidence supporting AIRT, it cannot be recommended for routine practice. PATIENT SUMMARY: Men with penile cancer who have involvement of the inguinal lymph nodes are at a high risk of cancer recurrence and death. We reviewed the literature to see if radiation treatment after removal of the nodes provided benefit. We did not find any good-quality evidence supporting this treatment, and hence it cannot be recommended.

T Cell Production of GM-CSF Protects the Host during Experimental Tuberculosis.

Although classically associated with myelopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) is increasingly recognized as being important for tuberculosis (TB) resistance. GM-CSF is expressed by nonhematopoietic and hematopoietic lineages following infection with Mycobacterium tuberculosis and is necessary to restrict M. tuberculosis growth in experimental models. Until the recent study by Rothchild et al. (mBio 8:e01514-17, 2017, https://doi.org/10.1128/mBio.01514-17), it was unknown whether GM-CSF-producing T cells contribute to TB resistance. Rothchild et al. identify which conventional and nonconventional T cell subsets produce GM-CSF during experimental TB, establish their protective nature using a variety of approaches, and provide a mechanistic basis for their ability to restrict M. tuberculosis growth. This commentary discusses the significance of these findings to basic and applied TB research. As translated to human disease, these findings suggest vaccine-mediated expansion of GM-CSF-producing T cells could be an effective prophylactic or therapeutic TB strategy.

Surface chemistry of cadmium sulfide magic-sized clusters: a window into ligand-nanoparticle interactions.

Optoelectronic properties of nanoparticles are intimately coupled to the complex physiochemical interplay between the inorganic core and the organic ligand shell. Magic-sized clusters, which are predominately surface atoms, provide a promising avenue to clarify these critical surface interactions. Whereas these interactions impact the surface of both nanoparticles and magic-sized clusters, we show here that only clusters manifest a shift in the excitonic peak by up to 0.4 eV upon solvent or ligand treatment. These results highlight the utility of the clusters as a probe of ligand-surface interactions.