Reversible Modulation of the Electronic and Spatial Environment around Ni(0) Centers Bearing Multifunctional Carbene Ligands with Triarylaluminum.

Designing and modulating the electronic and spatial environments surrounding metal centers is a crucial issue in a wide range of chemistry fields that use organometallic compounds. Herein, we demonstrate a Lewis-acid-mediated reversible expansion, contraction, and transformation of the spatial environment surrounding nickel(0) centers that bear N-phosphine oxide-substituted N-heterocyclic carbenes (henceforth referred to as (S)PoxIms). Reaction between tetrahedral (syn-κ-C,O-(S)PoxIm)Ni(CO)2 and Al(C6F5)3 smoothly afforded heterobimetallic Ni/Al species such as trigonal-planar {κ-C-Ni(CO)2}(µ-anti-(S)PoxIm){κ-O-Al(C6F5)3} via a complexation-induced rotation of the N-phosphine oxide moieties, while the addition of 4-dimethylaminopyridine resulted in the quantitative regeneration of the former Ni complexes. The corresponding interconversion also occurred between (SPoxIm)Ni(η2:η2-diphenyldivinylsilane) and {κ-C-Ni(η2:η2-diene)}(µ-anti-SPoxIm){κ-O-Al(C6F5)3} via the coordination and dissociation of Al(C6F5)3. The shape and size of the space around the Ni(0) center was drastically changed through this Lewis-acid-mediated interconversion. Moreover, the multinuclear NMR, IR, and XAS analyses of the aforementioned carbonyl complexes clarified the details of the changes in the electronic states on the Ni centers; i.e., the electron delocalization was effectively enhanced among the Ni atom and CO ligands in the heterobimetallic Ni/Al species. The results presented in this work thus provide a strategy for reversibly modulating both the electronic and spatial environment of organometallic complexes, in addition to the well-accepted Lewis-base-mediated ligand-substitution methods.

Return of the forgotten hero: the role of Y chromosome-encoded Zfy in male reproduction.

The Y-linked zinc finger gene ZFY is conserved across eutherians and is known to be a critical fertility factor in some species. The initial studies of the mouse homologues, Zfy1 and Zfy2, were performed using mice with spontaneous Y chromosome mutations and Zfy transgenes. These studies revealed that Zfy is involved in multiple processes during spermatogenesis, including removal of germ cells with unpaired chromosomes and control of meiotic sex chromosome inactivation during meiosis I, facilitating the progress of meiosis II, promoting spermiogenesis, and improving assisted reproduction outcomes. Zfy was also identified as a key gene in Y chromosome evolution, protecting this chromosome from extinction by serving as the executioner responsible for meiosis surveillance. Studies with targeted Zfy knock-outs revealed that mice lacking both homologues have severe spermatogenic defects and are infertile. Based on protein structure and in vitro assays, Zfy is expected to drive spermatogenesis as a transcriptional regulator. The combined evidence documents that the presence of at least one Zfy homologue is required for male fertility and that Zfy2 plays a more prominent role. This knowledge reinforces the importance of these factors for mouse spermatogenesis and informs our understanding of the human ZFY variants, which are homologous to the mouse Zfy1 and Zfy2.

Room-Temperature Reversible Chemisorption of Carbon Monoxide on Nickel(0) Complexes.

Chemisorption on organometallic-based adsorbents is crucial for the controlled separation and long-term storage of gaseous molecules. The formation of covalent bonds between the metal centers in the adsorbents and the targeted gases affects the desorption efficiency, especially when the oxidation state of the metal is low. Herein, we report a pressure-responsive nickel(0)-based system that is able to reversibly chemisorb carbon monoxide (CO) at room temperature. The use of N-heterocyclic carbene ligands with hemi-labile N-phosphine oxide substituents facilitates both the adsorption and desorption of CO on nickel(0) via ligand substitution. Ionic liquids were used as the reaction medium to enhance the desorption rate and establish a reusable system. These results showcase a way for the sustainable chemisorption of CO using a zero-valent transition-metal complex.

Two acquired mouse Y chromosome-linked genes, Prssly and Teyorf1, are dispensable for male fertility‡.

Prssly (Protease, serine-like, Chr Y) and Teyorf1 (Testis expressed, chromosome Y open reading frame 1) are two acquired single-copy genes located on the distal tip of the non-pairing short arm of the mouse Y chromosome adjacent to telomeric sequence. Both genes lack X chromosome-linked homologues and are expressed in testicular germ cells. We first performed analysis of Prssly and Teyorf1 genomic sequences and demonstrated that previously reported Prssly sequence is erroneous and the true Prssly sequence is longer and encodes a larger protein than previously estimated. We also confirmed that both genes encode pseudogenes that are not expressed in testes. Next, using CRISPR/Cas9 genome targeting, we generated Prssly and Teyorf1 knockout (KO) mice and characterized their phenotype. To create Prssly KO mice, we targeted the conserved exon 5 encoding a trypsin domain typical for serine proteases. The targeting was successful and resulted in a frame shift mutation that introduced a premature stop codon, with the Prssly KO males retaining only residual transcript expression in testes. The Teyorf1 targeting removed the entire open reading frame of the gene, which resulted in no transcript expression in KO males. Both Prssly KO and Teyorf1 KO males were fertile and had normal testis size and normal sperm number, motility, and morphology. Our findings show that Prssly and Teyorf1 transcripts with potential to encode proteins are dispensable for male fertility.

Loss of mouse Y chromosome gene Zfy1 and Zfy2 leads to spermatogenesis impairment, sperm defects, and infertility.

Using mice with Y chromosome deficiencies and supplementing Zfy transgenes, we, and others, have previously shown that the loss of Y chromosome Zfy1 and Zfy2 genes is associated with infertility and spermiogenic defects and that the addition of Zfy transgenes rescues these defects. In these past studies, the absence of Zfy was linked to the loss of other Y chromosome genes, which might have contributed to spermiogenic phenotypes. Here, we used CRISPR/Cas9 to specifically remove open reading frame of Zfy1, Zfy2, or both Zfy1 and Zfy2, and generated Zfy knockout (KO) and double knockout (DKO) mice. Zfy1 KO and Zfy2 KO mice were both fertile, but the latter had decreased litters size and sperm number, and sperm headshape abnormalities. Zfy DKO males were infertile and displayed severe spermatogenesis defects. Postmeiotic arrest largely prevented production of sperm and the few sperm that were produced all displayed gross headshape abnormalities and structural defects within head and tail. Infertility of Zfy DKO mice could be overcome by injection of spermatids or sperm directly to oocytes, and the resulting male offspring had the same spermiogenic phenotype as their fathers. The study is the first describing detailed phenotypic characterization of mice with the complete Zfy gene loss. It provides evidence supporting that the presence of at least one Zfy homolog is essential for male fertility and development of normal sperm functional in unassisted fertilization. The data also show that while the loss of Zfy1 is benign, the loss of Zfy2 is mildly detrimental for spermatogenesis.

Risk of drug-induced interstitial lung disease in hospitalised patients: a nested case-control study.

INTRODUCTION: Information on drug-induced interstitial lung disease (DILD) is limited due to its low incidence. This study investigated the frequencies of drug categories with potential risk in patients developing DILD during hospitalisation and analysed the risk of developing DILD associated with each of these drugs. METHODS: Using a Japanese national inpatient database, we identified patients without interstitial pneumonia on admission who developed DILD and required corticosteroid therapy during hospitalisation from July 2010 to March 2016. We conducted a nested case-control study; four controls from the entire non-DILD patient cohort were matched to each DILD case on age, sex, main diagnosis, admission year and hospital. We defined 42 classified categories of drugs with 216 generic names as drugs with potential risk of DILD, and we identified the use of these drugs during hospitalisation for each patient. We analysed the association between each drug category and DILD development using conditional logistic regression analyses. RESULTS: We retrospectively identified 2342 patients who developed DILD. After one-to-four case-control matching, 1541 case patients were matched with 5677 control patients. Six drug categories were significantly associated with the increased occurrence of DILD. These included epidermal growth factor receptor inhibitors (OR: 16.84, 95% CI 9.32 to 30.41) and class III antiarrhythmic drugs (OR: 7.01, 95% CI 3.86 to 12.73). Statins were associated with reduced risk of DILD (OR: 0.68, 95% CI 0.50 to 0.92). CONCLUSIONS: We demonstrated significant associations between various drug categories and DILD. Our findings provide useful information on drug categories with potential risk to help physicians prevent and treat DILD.

In-hospital mortality associated with community-acquired pneumonia due to methicillin-resistant Staphylococcus aureus: a matched-pair cohort study.

BACKGROUND: It remains unclear whether methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is associated with higher mortality compared with non-MRSA pneumonia. This study's objective was to compare outcomes including in-hospital mortality and healthcare costs during hospitalisation between patients with MRSA pneumonia and those with non-MRSA pneumonia. METHODS: Using a national inpatient database in Japan, we conducted a 1:4 matched-pair cohort study of inpatients with community-acquired pneumonia from 1 April 2012 to 31 March 2014. In-hospital outcomes (mortality, length of stay and healthcare costs during hospitalisation) were compared between patients with and without MRSA infection. We performed multiple imputation using chained equations followed by multivariable regression analyses fitted with generalised estimating equations to account for clustering within matched pairs. All-cause in-hospital mortality and healthcare costs during hospitalisation were compared for pneumonia patients with and without MRSA infection. RESULTS: Of 450,317 inpatients with community-acquired pneumonia, 3102 patients with MRSA pneumonia were matched with 12,320 patients with non-MRSA pneumonia. The MRSA pneumonia patients had higher mortality, longer hospital stays and higher costs. Multivariable logistic regression analysis revealed that MRSA pneumonia was significantly associated with higher in-hospital mortality compared with non-MRSA pneumonia (adjusted odds ratio = 1.94; 95% confidence interval: 1.72-2.18; p < 0.001). Healthcare costs during hospitalisation were significantly higher for patients with MRSA pneumonia than for those with non-MRSA pneumonia (difference = USD 8502; 95% confidence interval: USD 7959-9045; p < 0.001). CONCLUSIONS: MRSA infection was associated with higher in-hospital mortality and higher healthcare costs during hospitalisation, suggesting that preventing MRSA pneumonia is essential.

Early Arterial Embolization and Mortality in Mechanically Ventilated Patients With Hemoptysis: A Nationwide Retrospective Cohort Study.

OBJECTIVES: Hemoptysis, a symptom common across various respiratory diseases, can cause airway obstruction leading to a life-threatening condition. Arterial embolization has been used to control bleeding from the lower airways. However, limited studies have evaluated its effects on in-hospital mortality in patients with hemoptysis requiring mechanical ventilation. The objective of this study was to clarify whether early intervention by arterial embolization reduced mortality in mechanically ventilated patients with hemoptysis. DESIGN: Retrospective cohort study from July 2010 to March 2017. SETTING: More than 1,200 acute-care hospitals, comprising approximately 90% of all tertiary-care emergency hospitals in Japan. PATIENTS: The study cohort was patients with pulmonary diseases hospitalized for hemoptysis and mechanically ventilated within 2 days of admission. INTERVENTIONS: We compared patients who had undergone arterial embolization within 3 days of endotracheal intubation (early embolization group) with patients who did not (control group). MEASUREMENTS AND MAIN RESULTS: A total of 12,287 patients with hemoptysis requiring mechanical ventilation were analyzed. After 1:4 propensity score matching, there were 226 and 904 patients in the early embolization and control groups, respectively. The early embolization group was associated with lower 7-day and 30-day mortalities (7-d mortality: 1.3% vs 4.0%; odds ratio, 0.39; 95% CI, 0.16-0.97; p = 0.044 and 30-d mortality: 7.5% vs 16.8%; odds ratio, 0.45; 95% CI, 0.28-0.73; p = 0.001) and shorter duration of mechanical ventilation (median 6 d, interquartile range 4-13 d vs 8 d, interquartile range 4-19 d; p = 0.003) compared with the control group. CONCLUSIONS: Our results show that early intervention by arterial embolization may be effective in reducing 7-day and 30-day mortalities in patients with life-threatening hemoptysis requiring mechanical ventilation.

Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice.

Naftopidil, an α-1 adrenoceptor antagonist with few adverse effects, is prescribed for prostate hyperplasia. Naftopidil inhibits prostate fibroblast proliferation; however, its effects on lung fibroblasts and fibrosis remain largely unknown. Two normal and one idiopathic pulmonary fibrosis human lung fibroblast lines were cultured with various naftopidil concentrations with or without phenoxybenzamine, an irreversible α-1 adrenoceptor inhibitor. We examined the incorporation of 5-bromo-2'-deoxyuridine into DNA and lactic acid dehydrogenase release by enzyme-linked immunosorbent assay, cell cycle analysis by flow cytometry, scratch wound-healing assay, and mRNA expressions of type IV collagen and α-smooth muscle actin by polymerase chain reaction. Effects of naftopidil on bleomycin-induced lung fibrosis in mice were evaluated using histology, micro-computed tomography, and surfactant protein-D levels in serum. Naftopidil, dose-dependently but independently of phenoxybenzamine, inhibited 5-bromo-2'-deoxyuridine incorporation in lung fibroblasts. Naftopidil induced G1 cell cycle arrest, but lactic acid dehydrogenase release and migration ability of lung fibroblasts were unaffected. Naftopidil decreased mRNA expressions of type IV collagen and α-smooth muscle actin in one normal lung fibroblast line. Histological and micro-computed tomography examination revealed that naftopidil attenuated lung fibrosis and decreased serum surfactant protein-D levels in bleomycin-induced lung fibrosis in mice. In conclusion, naftopidil may have therapeutic effects on lung fibrosis.

Hospital Volume and Mortality following Diagnostic Bronchoscopy in Lung Cancer Patients: Data from a National Inpatient Database in Japan.

BACKGROUND: Recent advances in bronchoscopy utilizing endobronchial ultrasound (EBUS) as well as lung cancer therapy may have driven physicians to perform diagnostic bronchoscopy (DB) for high-risk patients. OBJECTIVES: The aim of this study was to clarify the relationship between hospital volume (HV) and outcomes of DB. METHODS: We collected data on inpatients with lung cancer who underwent DB from July 2010 to March 31, 2014. The annual HV of DB was classified as "very low" (≤50 cases/year), "low" (51-100 cases/year), "high" (101-300 cases/year), or "very high" (> 300 cases/year). The primary outcome was all-cause 7-day mortality after DB. Multivariable logistic regression fitted with a generalized estimation equation was performed to evaluate the association between HV and all-cause 7-day mortality after DB, adjusted for patient background factors. RESULTS: We identified a total of 77,755 eligible patients in 954 hospitals. All-cause 7-day mortality was 0.5%. Compared with the low-volume group, 7-day mortality was significantly lower in the high-volume group (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.52-0.92, p = 0.010), and a similar trend was shown in the very-high-volume group (OR = 0.67; 95% CI: 0.43-1.05, p = 0.080). Radial EBUS with the guide sheath method and EBUS-guided transbronchial needle aspiration showed a significantly lower 7-day mortality. CONCLUSIONS: All-cause 7-day mortality was inversely associated with HV. The risk of DB in patients with lung cancer should be recognized, and the exploitation of EBUS may help reduce mortality after DB.

Reference value for expiratory time constant calculated from the maximal expiratory flow-volume curve.

BACKGROUND: The expiratory time constant (RCEXP), which is defined as the product of airway resistance and lung compliance, enable us to assess the mechanical properties of the respiratory system in mechanically ventilated patients. Although RCEXP could also be applied to spontaneously breathing patients, little is known about RCEXP calculated from the maximal expiratory flow-volume (MEFV) curve. The aim of our study was to determine the reference value for RCEXP, as well as to investigate the association between RCEXP and other respiratory function parameters, including the forced expiratory volume in 1 s (FEV1)/ forced vital capacity (FVC) ratio, maximal mid-expiratory flow rate (MMF), maximal expiratory flow at 50 and 25% of FVC (MEF50 and MEF25, respectively), ratio of MEF50 to MEF25 (MEF50/MEF25). METHODS: Spirometric parameters were extracted from the records of patients aged 15 years or older who underwent pulmonary function testing as a routine preoperative examination before non-cardiac surgery at the University of Tokyo Hospital. RCEXP was calculated in each patient from the slope of the descending limb of the MEFV curve using two points corresponding to MEF50 and MEF25. Airway obstruction was defined as an FEV1/FVC and FEV1 below the statistically lower limit of normal. RESULTS: We retrospectively analyzed 777 spirometry records, and 62 patients were deemed to have airway obstruction according to Japanese spirometric reference values. The cut-off value for RCEXP was 0.601 s with an area under the receiver operating characteristic curve of 0.934 (95% confidence interval = 0.898-0.970). RCEXP was strongly associated with FEV1/FVC, and was moderately associated with MMF and MEF50. However, RCEXP was less associated with MEF25 and MEF50/MEF25. CONCLUSIONS: Our findings suggest that an RCEXP of longer than approximately 0.6 s can be linked to the presence of airway obstruction. Application of the concept of RCEXP to spontaneously breathing subjects was feasible, using our simple calculation method.

CISH is a negative regulator of IL-13-induced CCL26 production in lung fibroblasts.

BACKGROUND: Bronchial asthma is a chronic airway disease characterized by eosinophilic airway inflammation. Lung fibroblasts activated by IL-13 serve as important sources of chemokines, such as eotaxins, contributing to persistent eosinophilic inflammation. Src-homology 2-containing protein (CISH), belonging to the suppressor of cytokine signaling (SOCS) family, acts as a negative regulator of cytokine induction. The aim of this study was to elucidate the role of CISH in the production of eosinophil chemotactic chemokines in human lung fibroblasts. METHODS: Normal human lung fibroblasts were stimulated by IL-13, and global gene expression profile was assessed by cDNA microarray. Expression changes and downstream of IL-13 signaling were evaluated by quantitative RT-PCR, ELISA or western blotting. Loss- and gain-of-function analyses of CISH were performed by small interfering RNA and vector overexpression, respectively. RESULTS: Ingenuity pathway analysis revealed that IL-13 induced chemokine signaling, including the eotaxin family, while significantly suppressing IFN-α/ß signaling. Among eight SOCS family members, CISH was most strongly induced by IL-13 via phosphorylation of signal transducer and activator of transcription 6 (STAT6). Loss- and gain-of-function studies demonstrated that CISH negatively regulated the expression of CCL26. CONCLUSIONS: These findings suggest that CISH plays a key role in the eosinophilic inflammation associated with bronchial asthma by regulating IL-13-induced CCL26 production. Augmentation of CISH function could be a novel approach for treating eosinophilic inflammation in severe asthma.

TBX4 is involved in the super-enhancer-driven transcriptional programs underlying features specific to lung fibroblasts.

Lung fibroblasts participate in the pathogenesis of respiratory diseases, including lung cancer and pulmonary fibrosis. Although fibroblasts are ubiquitous constituents of various organs, their cellular diversity among different organs has been poorly characterized. Here, we aimed to investigate the distinct gene signature of lung fibroblasts that represents its pulmonary origin and the underlying gene regulatory networks. Promoter-level differential expression analysis by cap analysis of gene expression (CAGE) sequencing revealed distinct gene expression patterns of fibroblasts derived from different anatomical sites and identified 88 coding genes with higher expression in lung fibroblasts relative to other fibroblasts. Multiple key transcription factors important for lung mesenchyme development, including the T-box transcription factors TBX2, TBX4, and TBX5 were enriched in this lung-specific signature and were associated with super-enhancers. TBX4 showed highly specific expression in lung fibroblasts and was required for cell proliferation and collagen gel contraction capacity. Transcriptome analysis revealed that TBX4 could broadly regulate fibroblast-related pathways and partly contribute to super-enhancer-mediated transcriptional programs. Of pathological importance, lung fibroblast-specific genes were globally downregulated in lung cancer-associated fibroblasts (CAFs). Notably, TBX2, TBX4, and TBX5 were downregulated and hypermethylated in lung CAFs, suggesting an association between epigenetic silencing of these factors and phenotypic alteration of lung fibroblasts in cancer. Our study highlights the importance of T-box transcription factors, especially TBX4, and super-enhancers in the roles of lung fibroblasts in pulmonary physiology and pathogenesis.

Mechanism of Periostin Production in Human Bronchial Smooth Muscle Cells.

BACKGROUND: Asthma is a chronic airway inflammatory disease characterized by airway remodeling, in which the bronchial smooth muscle (BSM) cells play an important role. Periostin, a biomarker that reflects Th2-driven inflammatory diseases such as asthma, may play an important role in the asthmatic airway. Although periostin is mainly produced in airway epithelial cells and fibroblasts after interleukin (IL)-13 stimulation, whether BSM cells produce periostin remains unclear. Therefore, we investigated periostin production in BSM cells and the mechanisms involved. METHODS: Human BSM cells were cultured, and the effect of IL-13 stimulation on periostin production was evaluated using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). We evaluated the phosphorylation of signal transducer and activator of transcription factor 6 (STAT6), extracellular signal-regulated kinase (ERK)1/2, and Akt after IL-13 stimulation. Furthermore, using ELISA, we evaluated the influence of several phosphorylation inhibitors on periostin production. RESULTS: Periostin mRNA expression increased in a dose- and time-dependent manner after IL-13 stimulation; periostin production was induced 24 and 48 h after stimulation. IL-13 stimulation induced the phosphorylation of STAT6, ERK1/2, and Akt. IL-13-induced periostin production was attenuated by inhibiting STAT6 phosphorylation and strongly suppressed by inhibiting mitogen-activated protein kinase kinase 1/2 phosphorylation or phosphatidylinositol 3-kinase (PI3K) phosphorylation. CONCLUSIONS: BSM cells produced periostin after IL-13 stimulation, via the JAK/STAT6, ERK1/2, and PI3K/Akt pathways. Understanding the mechanism of periostin production in BSM cells may help to clarify asthma pathogenesis.

Venous thromboembolic events in patients with lung cancer treated with cisplatin-based versus carboplatin/nedaplatin-based chemotherapy.

An association between chemotherapy and venous thromboembolic events (VTEs) in patients with cancer is well established, with cisplatin (CDDP) being one of the most well-studied risk factors. However, whether CDDP is more strongly associated with occurrence of VTEs than carboplatin (CBDCA) or nedaplatin (CDGP) is controversial. Our purposes were to characterize patients with lung cancer and in-hospital VTEs, identify risk factors associated with VTEs, and compare the risks associated with CDDP-based versus CBDCA/CDGP-based chemotherapy. We retrospectively identified patients with lung cancer who underwent platinum-based chemotherapy from April 2012 to March 2015 from a national inpatient database in Japan. We used multivariable logistic regression analysis to analyze associations between various factors, including chemotherapy regimens and VTE. Of 235 104 eligible patients, 675 (0.29%) had VTEs after receiving platinum-based chemotherapy while hospitalized. Multivariable analysis showed that age, activity of daily living index, and invasive medical procedures were significant risk factors for the occurrence of VTE. Furthermore, CDDP-based chemotherapy was associated with a higher rate of VTE than CBDCA/CDGP-based chemotherapy (adjusted odds ratio: 1.35; 95% confidence interval: 1.08-1.68; P<0.01). In conclusion, CDDP-based chemotherapy is a stronger risk factor for VTEs than CBDCA/CDGP-based chemotherapy in patients with lung cancer.

Old age and underlying interstitial abnormalities are risk factors for development of ARDS after pleurodesis using limited amount of large particle size talc.

BACKGROUND AND OBJECTIVE: Talc pleurodesis is commonly performed to manage refractory pleural effusion or pneumothorax. It is considered as a safe procedure as long as a limited amount of large particle size talc is used. However, acute respiratory distress syndrome (ARDS) is a rare but serious complication after talc pleurodesis. We sought to determine the risk factors for the development of ARDS after pleurodesis using a limited amount of large particle size talc. METHODS: We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital. RESULTS: Twenty-seven and 35 patients underwent chemical pleurodesis using large particle size talc (4 g or less) or OK-432, respectively. Four of 27 (15%) patients developed ARDS after talc pleurodesis. Patients who developed ARDS were significantly older than those who did not (median 80 vs 66 years, P = 0.02) and had a higher prevalence of underlying interstitial abnormalities on chest computed tomography (CT; 2/4 vs 1/23, P < 0.05). No patient developed ARDS after pleurodesis with OK-432. This is the first case series of ARDS after pleurodesis using a limited amount of large particle size talc. CONCLUSION: Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis.

Mycobacterium heckeshornense lung infection diagnosed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

Identification of microorganisms by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been widely accepted. However, the significance of MALDI-TOF MS for identifying mycobacteria, particularly rare nontuberculous mycobacteria, has not been established. M. heckeshornense is one such bacteria, and distinguishing it from M. xenopi is difficult. The patient was a 40-year-old man with BehÒ«et's disease who had started treatment with prednisolone and azathioprine. A lung nodule in the right lower lobe was pointed out, and it increased in size 6 months later. Bronchoscopy was performed, and was culture positive for mycobacteria. It was identified as M. heckeshornense by MALDI-TOF MS with a score value of 1.928. Analysis of the 16S rRNA, rpoB, and hsp65 genes confirmed the result of MALDI-TOF MS. MALDI-TOF MS seems reliable for the diagnosis of M. heckeshornense infection.

Mouse Y-Encoded Transcription Factor Zfy2 Is Essential for Sperm Formation and Function in Assisted Fertilization.

Spermatogenesis is a key developmental process allowing for a formation of a mature male gamete. During its final phase, spermiogenesis, haploid round spermatids undergo cellular differentiation into spermatozoa, which involves extensive restructuring of cell morphology, DNA, and epigenome. Using mouse models with abrogated Y chromosome gene complements and Y-derived transgene we identified Y chromosome encoded Zfy2 as the gene responsible for sperm formation and function. In the presence of a Zfy2 transgene, mice lacking the Y chromosome and transgenic for two other Y-derived genes, Sry driving sex determination and Eif2s3y initiating spermatogenesis, are capable of producing sperm which when injected into the oocytes yield live offspring. Therefore, only three Y chromosome genes, Sry, Eif2s3y and Zfy2, constitute the minimum Y chromosome complement compatible with successful intracytoplasmic sperm injection in the mouse.

Testicular abnormalities in mice with Y chromosome deficiencies.

We recently investigated mice with Y chromosome gene contribution limited to two, one, or no Y chromosome genes in respect to their ability to produce haploid round spermatids and live offspring following round spermatid injection. Here we explored the normalcy of germ cells and Sertoli cells within seminiferous tubules, and the interstitial tissue of the testis in these mice. We performed quantitative analysis of spermatogenesis and interstitial tissue on Periodic acid-Schiff and hematoxylin-stained mouse testis sections. The seminiferous epithelium of mice with limited Y gene contribution contained various cellular abnormalities, the total number of which was higher than in the males with an intact Y chromosome. The distribution of specific abnormality types varied among tested genotypes. The males with limited Y genes also had an increased population of testicular macrophages and internal vasculature structures. The data indicate that Y chromosome gene deficiencies in mice are associated with cellular abnormalities of the seminiferous epithelium and some changes within the testicular interstitium.

Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan.

BACKGROUND: The optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy. METHODS: We retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, between July 2010 and March 2015. We extracted data on patient age, sex, comorbidities, and TNM classification at lung surgery; operative procedures, chemotherapy drugs, and radiotherapy during hospitalization; and discharge status. Recurrence-free survival was compared between the chemotherapy and chemoradiotherapy groups using multivariable Cox regression analysis. RESULTS: Median recurrence-free survival was 1146 days (95% confidence interval [CI], 885-1407) in the chemotherapy group (n = 489) and 873 days (95% CI, 464-1282) in the chemoradiotherapy group (n = 75). There was no significant difference between these after adjusting for patient backgrounds (hazard ratio, 1.29; 95% CI, 0.91-1.84). CONCLUSIONS: There was no significant difference in recurrence-free survival between patients with SCLC and N1-2 lymph node metastasis treated with postoperative adjuvant chemotherapy and chemoradiotherapy. Further randomized clinical trials are needed to address this issue.