Phylogenetic diversity, distribution, and gene structure of the pyruvic oxime dioxygenase involved in heterotrophic nitrification.

Some heterotrophic microorganisms carry out nitrification to produce nitrite and nitrate from pyruvic oxime. Pyruvic oxime dioxygenase (POD) is an enzyme that catalyzes the degradation of pyruvic oxime to pyruvate and nitrite from the heterotrophic nitrifying bacterium Alcaligenes faecalis. Sequence similarity searches revealed the presence of genes encoding proteins homologous to A. faecalis POD in bacteria of the phyla Proteobacteria and Actinobacteria and in fungi of the phylum Ascomycota, and their gene products were confirmed to have POD activity in recombinant experiments. Phylogenetic analysis further classified these POD homologs into three groups. Group 1 POD is mainly found in heterotrophic nitrifying Betaproteobacteria and fungi, and is assumed to be involved in heterotrophic nitrification. It is not clear whether group 2 POD, found mainly in species of the Gammaproteobacteria and Actinobacteria, and group 3 POD, found simultaneously with group 1 POD, are involved in heterotrophic nitrification. The genes of bacterial group 1 POD comprised a single transcription unit with the genes related to the metabolism of aromatic compounds, and many of the genes group 2 POD consisted of a single transcription unit with the gene encoding the protein homologous to 4-hydroxy-tetrahydrodipicolinate synthase (DapA). LysR- or Cro/CI-type regulatory genes were present adjacent to or in the vicinity of these POD gene clusters. POD may be involved not only in nitrification, but also in certain metabolic processes whose functions are currently unknown, in coordination with members of gene clusters.

Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients.

BACKGROUND: Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. METHODS: From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. RESULTS: There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. CONCLUSIONS: Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

Glue protein production can be triggered by steroid hormone signaling independent of the developmental program in Drosophila melanogaster.

Steroid hormones regulate life stage transitions, allowing animals to appropriately follow a developmental timeline. During insect development, the steroid hormone ecdysone is synthesized and released in a regulated manner by the prothoracic gland (PG) and then hydroxylated to the active molting hormone, 20-hydroxyecdysone (20E), in peripheral tissues. We manipulated ecdysteroid titers, through temporally controlled over-expression of the ecdysteroid-inactivating enzyme, CYP18A1, in the PG using the GeneSwitch-GAL4 system in the fruit fly Drosophila melanogaster. We monitored expression of a 20E-inducible glue protein gene, Salivary gland secretion 3 (Sgs3), using a Sgs3:GFP fusion transgene. In wild type larvae, Sgs3-GFP expression is activated at the midpoint of the third larval instar stage in response to the rising endogenous level of 20E. By first knocking down endogenous 20E levels during larval development and then feeding 20E to these larvae at various stages, we found that Sgs3-GFP expression could be triggered at an inappropriate developmental stage after a certain time lag. This stage-precocious activation of Sgs3 required expression of the Broad-complex, similar to normal Sgs3 developmental regulation, and a small level of nutritional input. We suggest that these studies provide evidence for a tissue-autonomic regulatory system for a metamorphic event independent from the primary 20E driven developmental progression.

[Acute hospital collaboration with the region].

The palliative care team of Tokai University Hospital began its activities in 2004. After several changes in its organization, the activities of the palliative care team have become well known, and this department has become very active. Palliative care at our hospital has now broadened its scope and now includes both inpatients and outpatients. Initially, the patients primarily consisted of terminal-stage cancer patients, but in recent years patients who are being treated for cancer have also been included in the palliative care department. In terms of our collaboration with the region, the health care providers responsible for palliative care are making continued efforts to establish good relationships through regular scheduled palliative care training workshops and study sessions. Regional collaborations with oncologists is the ultimate/primary goal. As an educational institution we conduct clinical practical training and clinical training in core hospitals and private practices with medical students and junior resident physicians. However, few of these training institutions are home-care-supporting clinics or home-care-supporting hospitals. It remains unclear whether medical students and resident physicians are involved in home care. Knowledge of palliative care has gradually increased among the health care providers at our hospital. However, the dissemination of knowledge about home care among medical students, resident physicians, and oncologists is found to be lacking; hence, we have made this our goal. Another goal of ours would be to train existing physicians to equip them with knowledge and experience necessary for dealing with home care.

[Thoracoscopic lobectomy as minimally invasive surgery].

There has always been a conflict between the proposition that surgical methods for treating lung cancer should completely remove the lesion and the seemingly contradictory proposition that they should be as minimally invasive as possible. The achievement of radicality has been pursued by specializing, and began in 1933 when Graham performed total pneumonectomy for lung cancer. In 1960, the current surgical "gold standard" for lung cancer was reached when anatomical lobectomy and lymph node dissection were performed by Cahan, and subsequently called "radical lobectomy." The pursuit of less invasiveness began in the early 1980s, after the achievement of radicality, and thoracoscopic lobectomy has been developed as a major advance. Thoracoscopic lobectomy differs only in the method of accessing the pleural cavity: the surgical procedure within the pleural cavity does not differ from the procedure for radical lobectomy. In addition, the outcome of patients who have undergone thoracoscopic lobectomy as a form of minimally invasive surgery has been reported to be better than that after open lobectomy, and it is now clear that thoracoscopic lobectomy contributes to improving patients' postoperative quality of life. Accumulating additional cases and further study will be necessary in the future.

Refractory Pneumothorax Due to Cystic Pulmonary Metastasis of a Lowgrade Endometrial Stromal Sarcoma: A Case Report.

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine neoplasm. Computed tomography (CT) revealed the presence of multiple small bilateral pulmonary nodules in a 58-year-old woman 1 year after surgery for LG-ESS; the clinical diagnosis was pulmonary metastasis. Hormone therapy with progesterone was initiated, after which most of the solid nodules disappeared and some transformed into cystic lesions. Seven years after hormone therapy, the patient experienced repeated pneumothorax. The cause of the pneumothorax was perforation of a metastatic focus within the wall of a small subpleural cyst that was not evident on CT images.

Does childhood maltreatment affect hikikomori via traits of modern-type depression?

BACKGROUND: In the 1990s, the concepts of hikikomori and modern-type depression (MTD) emerged in Japan. Hikikomori is a condition of social avoidance or isolation, characterized by staying at home and being physically isolated for at least six months. MTD is characterized by depressive symptoms-mainly in stressful work or school situations during adolescence and early adulthood-which tend to rapidly reduce or disappear after leaving the stressful situation. We hypothesized that childhood maltreatment can form MTD traits that lead to hikikomori. METHODS: As a first step, we conducted a multigroup path analysis between childhood maltreatment, MTD traits, and physical isolation in the hikikomori group. This study utilized the nine-item Patient Health Questionnaire (PHQ-9), Home Environment Questionnaire (HEQ), 22-item Tarumi Modern-Type Depressive Trait Scale (TACS-22), 25-item Hikikomori Questionnaire (HQ-25), and Hamilton Depression Rating Scale (HDRS). The HQ-25 contains three factors: physical isolation, lack of socialization, and lack of emotional support. RESULTS: The hikikomori group included 92 patients and the control group comprised 137 healthy individuals. All total and subscale scores of PHQ-9, HEQ, TACS-22, HQ-25, and HDRS were significantly higher in the hikikomori group than in the control group. The risk model of childhood maltreatment for physical isolation via MTD traits obtained good fit with a goodness-of-fit index of.982. LIMITATIONS: The study's limitations were its sample selection bias, cross-sectional design, and use of self-report scales. CONCLUSIONS: Our findings support the hypothesis that childhood maltreatment is an important risk factor for hikikomori via MTD traits.

Significance of ZO-1, an Intercellular Adhesion Molecule, as a Prognostic Marker in Lung Adenocarcinoma.

In epithelial tissues, intercellular adhesion structures are formed between adjacent cells via intercellular adhesion factors, such as zonula occludens (ZO-1), to maintain the structure and function of tissues and organs, thereby contributing to homeostasis. Epithelial cells are polarized into apical and basal regions by tight junctions (TJs), a type of intercellular adhesion structure, and thus, their intracellular organelles are asymmetrically distributed. Normal epithelial cells maintain their cellular function by controlling cytoskeletal reorganization, motility, and division by maintaining asymmetry in their intracellular organelles. Among the features common to many cancer tissues are abnormalities in cell polarity and intercellular adhesion. Lung adenocarcinoma consists of a mixture of five different histologic types that can be distinguished in the same section: lepidic, papillary, acinar, micropapillary, and solid patterns. Therefore, it is often difficult to accurately assess histological images because the staining differs according to the histological types. In the present study, we evaluated ZO-1 staining based on histological features observed in a single section and examined its relationship to clinicopathological features. In non-tumor areas, ZO-1 was expressed on the plasma membrane and in the cytoplasm of normal alveolar epithelial cells. However, in tumor areas, ZO-1 staining was mainly localized in the cytoplasm and on the plasma membrane only in a few cells. ZO-1-negative cases tended to have poorer prognoses in all histological types, with a poorer prognosis in the solid pattern. These results suggest that ZO-1 expression in solid-pattern lung adenocarcinoma may be a useful prognostic marker.

Using hemoglobin vesicles to treat operative hemorrhagic shock after pneu- monectomy in dog models: an experimental study.

Hemoglobin vesicles (HbVs), considered as red blood cell substitutes, are liposomes encapsulating purified hemoglobin, with a phospholipid bilayer membrane (diameter: 250 nm; P50, 28 Torr). In this study, we aimed to investigate HbV function during hemorrhagic shock in lung resection and analyze the details of oxygen delivery. Left pneumonectomy was performed in dogs under mechanical ventilation, followed by rapid exsanguination of approximately 30% of the total circulating blood volume, which led to shock, reducing the mean arterial pressure (MAP) by approximately 60% of baseline. Subsequently, either 5% human serum albumin (HSA) or HbVs suspended in 5% HSA were infused for resuscitation. The MAP only recovered to 75% of baseline after HSA administration, but fully recovered (100%) after HbV administration, with significant differences between the groups (P < 0.005). Oxygen delivery was restored in the HbV group and was significantly higher than that in the HSA group (P < 0.0001). The infusion of HbVs dispersed in a 5% HSA solution compensated for the rapid loss of approximately 30% of the total circulating blood volume in a dog pneumonectomy model, even with impaired lung function. Thus, HbVs can be used for resuscitation from hemorrhagic shock during thoracic surgery.

Minimally invasive surgery for anterior flail chest injury in the acute phase: series of 10 cases.

OBJECTIVE: Anterior flail chest frequency represents a significant case of ventilator insufficiency. Surgical stabilization of acute phase of trauma is considered to effectively shorten the period of ventilation compared to conservative treatment using mechanical ventilation. We have applied minimally invasive surgery to stabilize the injured chest wall. METHODS: Surgical stabilization of predominantly anterior flail chest segments was performed using one or two bars as per the Nuss procedure, during the acute phase of chest trauma. Data from all patients were examined. RESULTS: Ten patients received surgical stabilization using the Nuss method between 1999 and 2021. All patients had already been mechanically ventilated prior to surgery. The mean period from trauma to surgery was 4.2 days (range, 1-8 days). The number of bars used was one for 7 patients, and two for 3 patients. The mean operation time was 60 min (range, 25-107 min). All patients were extubated from artificial respiration without surgical complications or mortality. Mean total ventilation period was 6.5 days (range, 2-15 days). All bars were removed in a subsequent surgery. No collapses or fracture recurrences were observed. CONCLUSION: This method is simple and effective for fixed anterior dominant frail segment.

[Rectal tenesmus due to tumor invasion into the pelvic cavity responding favorably to antiarrhythmic drug therapy].

We experienced 3 patients(Cases 1, 3, and 4)with pelvic tumor-related rectal tenesmus showing favorable responses to antiarrhythmic drugs. Based on this experience, we administered antiarrhythmic drugs preferentially to 2 others with tumor derived rectal tenesmus(Cases 2 and 5), and again obtained favorable responses. These 5 patients(1 man, 4 women)were 28-89(mean 58)years of age. The primary lesion was cervical cancer in 3 patients, ovarian cancer in 1, and bladder cancer in 1. In the 3 with cervical cancer, the tumor had directly infiltrated the rectum and vulva. The patient with ovarian cancer had a residual tumor in the Douglas pouch postoperatively. The patient with bladder cancer had undergone total cystectomy and urinary diversion using an ileal conduit at another institution. All 5 patients complained of a frequent desire to defecate without feces(rectal tenesmus). Their rectal tenesmus was attributed to pelvic neurological dysfunction around the rectum. Drug therapy was initiated with oral mexiletine hydrochloride(Mexitil)150 mg in 3 divided doses in 4 patients and with continuous infusion of intravenous lidocaine 2%(Xylocaine)500mg/day in the other(Case 2). None had adverse reactions; all 5 experienced palliation of symptoms and improved quality of life.

Development of a Subclinical Dissociation Scale by Comparing Healthy Controls with Patients.

We developed a Subclinical Dissociation Scale by comparing healthy controls with patients with post-traumatic stress disorder (PTSD) or dissociative disorder. The Dissociative Experiences Scale, Subclinical Dissociation Scale, and General Health Questionnaire were completed by 441 healthy Japanese adolescents (mean age, 19.9 years) and 23 psychiatric inpatients (mean age, 28.8 years) diagnosed with PTSD or dissociative disorder. The initial Subclinical Dissociation Scale included 52 items grouped into five factors: F1, absentmindedness (14 items); F2, immersion or preoccupation (15 items); F3, temporary amnesia (10 items); F4, feelings of unreality (eight items); and F5, feelings of alienation (five items). Factor and correlation analyses revealed the validity and reliability of the Subclinical Dissociation Scale. The final version of the scale that comprised three factors (F1, F2, and F4) and 37 items underwent logistic regression and receiver operating characteristic (ROC) curve analyses to compare healthy controls with patients with PTSD or dissociative disorder. The ROC curve analysis using the Youden Index indicated a cut-off score of 18 for the borderline or abnormal range, which was calculated using the following formula: "(F1) + (F4) - (F2)." This study provides evidence of the partial test-retest reliability and con current validity of the Subclinical Dissociation Scale.

Thymic Dedifferentiated Liposarcoma Having a Leiomyosarcomatous Dedifferentiated Component.

We report an extremely rare case of 42-year-old man, d iagnosed with thymic dedifferentiated liposarcoma (DDL) having a leiomyosarcomatous dedifferentiated component. The tumor was composed of atypical spindle cells. The morphological atypia was also observed around thymic adipose tissue. Immunohistochemically, the spindle cells were positive for desmin, smooth muscle actin, MDM2 and CDK4. MDM2 and CDK4 were also positive for the thymic adipose tissue. MDM2 amplification was confirmed by fluorescence in situ hybridization. Although there are some reports of mediastinal leiomyosarcoma, DDL may be overlooked. For accurate diagnosis of mediastinal mesenchymal tumor, careful observation of thymic adipose tissue is required with immunohistochemical study.

Enteric-type thymic adenocarcinoma: a case report and literature review focusing on prognosis based on histological subtypes.

Thymic adenocarcinoma is a rare disease and enteric-type thymic adenocarcinoma is even more rarely found. We report a resected case of a non-mucinous, enteric-type thymic adenocarcinoma in a 53-year-old woman. The operation was performed by median sternotomy, and the tumor was stage II in the Masaoka classification. Six months after the operation, recurrence-free follow-up is currently underway. Knowledge of enteric-type thymic adenocarcinoma can prevent misdiagnosis of metastatic tumors. We also determined the prognosis of enteric-type thymic adenocarcinoma based on histological subtypes through our literature review.

Protective effect of ebselen on bleomycin-induced lung fibrosis: analysis of the molecular mechanism of lung fibrosis mediated by oxidized diacylglycerol.

The molecular mechanisms underlying the development of pulmonary fibrosis remain unknown, and effective treatments have not yet been developed. It has been shown that oxidative stress is involved in lung fibrosis. Oxidized diacylglycerol (DAG) produced by oxidative stress is thought to play an important role in lung fibrosis. This study assessed the effect of oxidized DAG in an animal model of pulmonary fibrosis induced by aspiration of bleomycin (BLM) into the lungs. The inhibitory effect of ebselen on pulmonary fibrosis was also investigated. In lung fibrotic tissue induced by BLM, an increase in lipid peroxides and collagen accumulation was observed. Moreover, the levels of oxidized DAG, which has strong protein kinase C (PKC) activation activity, were significantly increased over time following the administration of BLM. Western blotting showed that phosphorylation of PKCα and δ isoforms was increased by BLM. Oral administration of ebselen significantly suppressed the increase in oxidized DAG induced by BLM and improved lung fibrosis. PKCα and δ phosphorylation were also significantly inhibited. The mRNA expression of α-smooth muscle actin and collagen I (marker molecules for fibrosis), as well as the production of transforming growth factor-ß and tumor necrosis factor-α(a potentially important factor in the fibrotic process), were increased by BLM and significantly decreased by ebselen. The administration of BLM may induce lipid peroxidation in lung tissue, while the oxidized DAG produced by BLM may induce overactivation of PKCα and δ, resulting in the induction of lung fibrosis.

Early reperfusion with hemoglobin vesicles into tracheal subepithelial capillaries in a mouse tracheal transplant model.

Hemoglobin vesicles (HbVs), liposomes containing concentrated hemoglobin extracted from outdated human red blood cells (RBC), are artificial oxygen carriers with a small particle size. To evaluate the reperfusion of capillaries with HbVs in a tracheal transplant model and compare it with that of RBC. Isogenic mice were used as donors and recipients in a parallel trachea transplant model. Both ends of the donor trachea were anastomosed end-laterally to the recipient trachea to form in parallel. After transplantation, 0.3 mL of HbV solution (Hb concentration, 10 g/dL) was administered via the tail vein. The recipients were euthanized 1, 4, 6, and 8 h after surgery (n = 5 in each group). The tracheas were harvested, and tracheal subepithelial capillaries (SEC) reperfusion was histologically evaluated. A significant number of particles defined as HbV by electron microscopy were observed in the SEC of the grafted tracheas 4 h after the transplant surgery and HbV administration when no RBC were found in the SECs. The number increased 6 and 8 h later. Our findings suggest that HbVs, which are smaller than RBC, can reperfuse the capillaries of grafts earlier than RBCs after transplantation and contribute to the oxygenation of transplanted tissues.

[A case of pain management using transdermal fentanyl patches for peritoneal carcinomatosis in a patient with small intestine stoma].

We experienced a patient with an ileal artificial anus who suffered from abdominal pain caused by peritoneal dissemination of ovarian cancer, for which slow-release oxycodone was ineffective, but fentanyl patch proved effective. The patient was a 28-year-old female who developed abdominal pain caused by peritoneal dissemination on postoperative day 60 after radical hysterectomy and colostomy. For pain relief, administration of 10-mg slow-release oxycodone and 180-mg loxoprofen sodium was begun. When the dose was increased to 25 mg on postoperative day 240, the slow-release oxycodone in its original form was confirmed in feces from the artificial anus.When the same drug was changed to a fentanyl patch(12. 5 mg/hr), the pain was relieved. A palliative care doctor needs much knowledge regarding the changes in the patient's body with the progress and treatment of cancer, in addition to the drug mechanism.

Assessment of dyspnea in terminally ill cancer patients: role of the thoracic surgeon as a palliative care physician.

BACKGROUND: Many cancer patients suffer from rapidly-progressing dyspnea that is difficult to relieve. METHODS: The subjects were 26 patients who had dyspnea that was difficult to relieve. The Numeric Rating Scale was used to evaluate their dyspnea. For all patients, the cause of the dyspnea was investigated by CT and x-rays. RESULTS: The principal causes of the dyspnea were pleural effusion that increased daily, complications from pneumonia, massive ascites, multiple metastatic lung tumors and atelectasis, recurrent laryngeal nerve paralysis and narrowing secondary airway compression. Dyspnea was caused by a variety of conditions that overlapped over time, intensifying patients' discomfort. Among 14 patients for whom we recommended treatment with sedation, only 8 of them consented. Among the patients who were treated with sedation, the median interval between the exacerbation of dyspnea and death was 16 days; among non-sedated patients it was 18 days. CONCLUSIONS: Palliative care physicians who specialize in the respiratory system can, to some extent, predict the occurrence of rapidly progressive dyspnea in cancer patients. It is important to explain the methods of relieving dyspnea to the patient, the patient's family, and the oncologist early, so that decisions on how to manage dyspnea can be made in advance.

A Case of Thoracolithiasis Extracted with a Thoracoscope.

We report on an 81-year-old male patient in whom chest computed tomography during follow-up for extramammary Paget's disease revealed a nodule in the right thoracic cavity. Because he had been taking methotrexate for rheumatoid arthritis, the possibility of methotrexate-associated lymphoproliferative lung disease was considered and methotrexate was discontinued as a precaution. No calcification was found inside the nodule, and there was no change in its size or position for 6 months. The patient had a history of malignant tumor, so thoracoscopic surgery was performed for diagnostic purposes. A free white nodule was found in the right thoracic cavity and was subsequently removed. The pathological diagnosis was thoracolithiasis; although the nodule had not moved since its discovery, movement was suspected to have occurred 3 years prior. Although thoracolithiasis is rare, it should be considered as a differential diagnosis for nodules at the end of the lung field and on the diaphragm.

Pulmonary glomus tumor observed for 6 years: A case report.

Glomus tumors are rarely developed in the lung. We report a case of a pulmonary glomus tumor that was observed for a long period. The patient was a 50-year-old man. Chest computed tomography showed a 6 mm nodule in the left lower lobe. The patient requested follow-up observation. The nodule gradually increased and was resected 6 years later. Pulmonary partial resection was performed thoracoscopy. The lesion was diagnosed as a glomus tumor with no malignant features. Pulmonary glomus tumors are rare and difficult to diagnose before resection. However, care is necessary as they may be malignant.