Amyand's Hernia diagnosed preoperatively via a CT scan: A case report.

Amyand's hernia is a rare type of inguinal hernia characterized by the presence of the vermiform appendix within the hernia sac. It was named after Claudius Amyand who performed the world's first successful appendectomy on an 11-year-old boy with a right inguinal hernia in 1735 and discovered a herniated appendix during surgery. This condition warrants urgent surgical treatment, with the type of surgical intervention depending on the appendix's condition. However, the nonspecific clinical presentation often complicates the preoperative diagnosis, emphasizing the critical role of imaging in surgical planning. Herein, we present the case of a 74-year-old male who presented with fever, inguinal swelling, and discomfort. Clinical suspicion of inguinal and scrotal inflammation prompted us to perform a prompt CT scan. This radiological evaluation led to a preoperative diagnosis of a Type 3 Amyand's hernia. This case highlights the significance of CT scans in the accurate and timely diagnosis of Amyand's hernia. Distinguishing between various types of Amyand's hernia is pivotal as it profoundly influences surgical decision-making and postoperative outcomes. By sharing this case, we contribute to current knowledge about Amyand's hernia, increase clinical awareness of the condition, and emphasize the crucial role of imaging in its management.

Factors contributing to prolonged operative time for laparoscopic cholecystectomy performed by trainee surgeons: a retrospective single-center study.

PURPOSE: Laparoscopic cholecystectomy for a benign disease is often the initial endoscopic surgery performed by trainee surgeons. However, a lack of surgical experience is associated with prolonged operative times, which may increase the risk of postoperative complications and poor outcomes. This study aimed to identify the factors associated with prolonged operative times for laparoscopic cholecystectomy performed by inexperienced surgeons. METHODS: This retrospective single-center study was conducted between January 2018 and December 2023. We performed a multivariate analysis to identify the factors associated with prolonged operative time by analyzing elective cases of laparoscopic cholecystectomy performed by surgeons with limited experience. RESULTS: The study included 323 patients, subjected to a median operative time of 89 min. Multivariate analysis identified that patient characteristics such as male sex, increased body mass index, and a history of conservative treatment for cholecystitis, as well as operating surgeon's post-graduation years (< 4 years), and an attending surgeon without endoscopic surgical skill certification from the Japan Society of Endoscopic Surgery, were independent risk factors for a prolonged operative time. CONCLUSION: Our findings suggest that endoscopic surgical skill-certified attending surgeons have excellent coaching skills and mitigate the operative time for elective cholecystectomy.

Prosaposin is a novel coenzyme Q10-binding protein.

Coenzyme Q10 (CoQ10) is essential for mitochondrial ATP production and functions as an important antioxidant in every biomembrane and lipoprotein. Due to its hydrophobicity, a binding and transfer protein for CoQ10 is plausible, and we previously described saposin B as a CoQ10-binding and transfer protein. Here, we report that prosaposin, the precursor of saposin B, also binds CoQ10. As prosaposin is both a secretory protein and integral membrane protein, it is ubiquitous in the body. Prosaposin was isolated from human seminal plasma, and CoQ10 was extracted from hexane solution into the water phase. It was additionally found that immunoprecipitates of mouse brain cytosol generated using two different anti-prosaposin antibodies contained coenzyme Q9. Furthermore, mouse liver cytosol and mouse kidney cytosol also contained prosaposin-coenzyme Q9 complex. These results suggest that prosaposin binds CoQ10 in human cells and body fluids. The significance and role of the Psap-CoQ10 complex in vivo is also discussed.

Retrospective analysis of urinary tract infections in long-term care facilities in Japan: Insights from physical examination-based diagnosis.

Objectives: Multidrug-resistant (MDR) bacterial infections are highly prevalent among long-term care facility (LTCF) residents, and are thus important targets for antimicrobial stewardship. Diagnoses of urinary tract infections (UTIs), which are associated with antimicrobial use in these facilities, are not always made by physicians. Past epidemiologic studies have included asymptomatic bacteriuria together with UTIs. The National Healthcare Safety Network has initiated a surveillance program to identify the causative organisms of UTIs in LTCF residents. In Japan, medical care for these residents is provided through in-person physician visits; however, limited related data are available. Therefore, we investigated the organisms causing UTIs and their drug susceptibility among LTCF residents in central Japan, and examined the prevalence of multidrug resistance, its risk factors, and correlations with clinical outcomes. Methods: We retrospectively evaluated clinical and urine culture data of LTCF residents with physician-diagnosed UTIs between April 1, 2019, and April 30, 2022. Results: The detection rate of multidrug-resistant organisms was high, with Escherichia coli being the most prevalent. Ceftriaxone was frequently used for initial therapy. The initial antimicrobial agents were significantly less active against MDR pathogens than non-MDR pathogens. Most residents continued to receive the initial agents regardless of culture results. Nonetheless, differences in the therapy duration, relapse and hospitalization rates, and death rate within 28 days between the multidrug-resistant and non-multidrug-resistant groups were not significant. Conclusions: Antimicrobial stewardship is essential for reducing antimicrobial use and selective pressure in LTCFs in Japan; however, more specific data are needed for its effective implementation.

Recurrent cholangitis and bacteraemia due to Edwardsiella tarda: a case report.

Edwardsiella tarda is typically isolated from aquatic environments. It rarely causes infections in humans. Edwardsiella tarda infections in humans result from the consumption of infected or contaminated food. Here, we present a case of recurrent cholangitis and bacteraemia associated with E. tarda. An 82-year-old man with no history of seafood inoculation was admitted to our hospital because of difficulty in moving his body. The patient was diagnosed with cholangitis, and the blood culture revealed the presence of E. tarda. The patient underwent bile duct stenting and received antibiotic therapy for 14 days. Forty-four days after discharge, cholangitis recurred, and blood culture again showed the presence of E. tarda. The patient underwent bile duct stenting and antibiotic therapy for 11 days. No cholangitis or bacteraemia associated with E. tarda was observed in the following 3 years. Our case strongly suggests that colonization with E. tarda results in recurrent cholangitis and bacteraemia.

Acceleration of Protein Degradation by 20S Proteasome-Binding Peptides Generated by In Vitro Artificial Evolution.

Although the 20S core particle (CP) of the proteasome is an important component of the 26S holoenzyme, the stand-alone 20S CP acts directly on intrinsically disordered and oxidized/damaged proteins to degrade them in a ubiquitin-independent manner. It has been postulated that some structural features of substrate proteins are recognized by the 20S CP to promote substrate uptake, but the mechanism of substrate recognition has not been fully elucidated. In this study, we screened peptides that bind to the 20S CP from a random eight-residue pool of amino acid sequences using complementary DNA display an in vitro molecular evolution technique. The identified 20S CP-binding amino acid sequence was chemically synthesized and its effects on the 20S CP were investigated. The 20S CP-binding peptide stimulated the proteolytic activity of the inactive form of 20S CP. The peptide bound directly to one of the α-subunits, opening a gate for substrate entry on the α-ring. Furthermore, the attachment of this peptide sequence to α-synuclein enhanced its degradation by the 20S CP in vitro. In addition to these results, docking simulations indicated that this peptide binds to the top surface of the α-ring. These peptides could function as a key to control the opening of the α-ring gate.

Continuous monitoring of activity and vital signs with load cells under the bed legs in advanced cancer patients: a prospective exploratory observational study-can it represent performance status?

BACKGROUND: Activity levels of patients often scaled as performance status (PS) is the most important scale in oncology populations for treatment decisions and prognosis prediction. However, it is usually subjective and open to bias. The need for more objective and reliable assessment tools is mandatory for safe and effective oncology practice. To investigate the reliability of continuous vital and activity evaluation monitored by bed sensor systems in advanced cancer patients, we conducted a cohort pilot study in hospitalized cancer patients under several PS conditions. METHODS: Adult patients, either admitted in the oncology department or palliative care unit, were enrolled in the study after written informed consent. Continuous monitoring for 48 hours from the first night of admission was performed without any restrictions on the patients. Calculated acceleration of movement [activity index (ACI)], % time on bed and number of bed leave in an 8-hour period, as well as other vital signs were monitored. Analysis focused on change of PS to 3, a standard cut-off for curative cancer treatment and PS4, vital for prognosis assessment. RESULTS: Nineteen patients' data were analyzed. In PS4 palliative care patients, ACI was significantly low and % time on bed was high from PS3 palliative care patients. Instabilities of respiratory rate, respiratory tidal weight and heart rate were significantly higher in palliative care patients (PS3, PS4) compared with oncology patients (PS1, PS2). CONCLUSIONS: This result, though in need of larger trials, shows possibilities for continuous objective monitoring of patients in bed for PS assessment in advanced cancer patients.

[A Case of Rectal Cancer Suspectedly Recurred Seventeen Years after EMR].

We report a case of a 73-year-old man who underwent endoscopic mucosal resection (EMR) for early rectal cancer(i ntramucosal cancer)at other hospital 17 years ago. Ten years later, he underwent a total colonoscopy, which showed no recurrence of the tumor. Twelve years later, a mass with calcification was incidentally detected in front of the sacrum, which was diagnosed as a benign tumor at that time. Seventeen years later, he presented with constipation and diarrhea, and was detected of a sub-circumferential tumor in the rectum by a total colonoscopy. Biopsy revealed that the tumor was malignancy. CT showed a mass in the left lateral liver lobe. The mass was suspected of metastasis. Laparoscopic super lower anterior resection was performed for rectal cancer, and pathological examination showed that the tumor was pT4a, N3, M1(H), Stage Ⅳa. One month after surgery, laparoscopic hepatectomy was performed for liver metastasis. Six months after surgery, CT showed multiple lung metastases. He continues to undergo chemotherapy. Although this case was treated with EMR for intramucosal carcinoma, clinical history and pathological findings suggested local recurrence.

Analysis of Environmental and Pathogenic Bacteria Attached to Aerosol Particles Size-Separated with a Metal Mesh Device.

Metal mesh devices (MMDs) are novel materials that enable the precise separation of particles by size. Structurally, MMDs consist of a periodic arrangement of square apertures of characteristic shapes and sizes on a thin nickel membrane. The present study describes the separation of aerosol particles using palm-top-size collection devices equipped with three types of MMDs differing in pore size. Aerosols were collected at a farm located in the suburbs of Nairobi, Kenya; aerosol particles were isolated, and pathogenic bacteria were identified in this microflora by next-generation sequencing analysis. The composition of the microflora in aerosol particles was found to depend on particle size. Gene fragments were obtained from the collected aerosols by PCR using primers specific for the genus Mycobacterium. This analysis showed that Mycobacterium obuense, a non-tuberculous species of mycobacteria that causes lung diseases, was present in these aerosols. These findings showed that application of this MMD analytical protocol to aerosol particles can facilitate the investigation of airborne pathogenic bacteria.

Combination Therapy of High-flow Nasal Cannula and Upper-body Elevation for Postoperative Sleep-disordered Breathing: Randomized Crossover Trial.

BACKGROUND: The low acceptance rate of continuous positive airway pressure therapy in postoperative patients with untreated obstructive sleep apnea (OSA) indicates the necessity for development of an alternative postoperative airway management strategy. The authors considered whether the combination of high-flow nasal cannula and upper-body elevation could improve postoperative OSA. METHODS: This nonblinded randomized crossover study performed at a single university hospital investigated the effect on a modified apnea hypopnea index, based exclusively on the airflow signal without arterial oxygen saturation criteria (flow-based apnea hypopnea index, primary outcome), of high-flow nasal cannula (20 l · min-1 with 40% oxygen concentration) with and without upper-body elevation in patients with moderate to severe OSA. Preoperative sleep studies were performed at home (control, no head-of-bed elevation) and in hospital (30-degree head-of-bed elevation). On the first and second postoperative nights, high-flow nasal cannula was applied with or without 30-degree head-of-bed elevation, assigned in random order to 23 eligible participants. RESULTS: Twenty-two of the 23 (96%) accepted high-flow nasal cannula. Four participants resigned from the study. Control flow-based apnea hypopnea index (mean ± SD, 60 ± 12 events · h-1; n = 19) was reduced by 15 (95% CI, 6 to 30) events · h-1 with head-of-bed elevation alone (P = 0.002), 10.9 (95% CI, 1 to 21) events · h-1 with high-flow nasal cannula alone (P = 0.028), and 23 (95% CI, 13 to 32) events · h-1 with combined head-of-bed elevation and high-flow nasal cannula (P < 0.001). Compared to sole high-flow nasal cannula, additional intervention with head-of-bed elevation significantly decreased flow-based apnea hypopnea index by 12 events · h-1 (95% CI, 2 to 21; P = 0.022). High-flow nasal cannula, alone or in combination with head-of-bed elevation, also improved overnight oxygenation. No harmful events were observed. CONCLUSIONS: The combination of high-flow nasal cannula and upper-body elevation reduced OSA severity and nocturnal hypoxemia, suggesting a role for it as an alternate postoperative airway management strategy.

Extrapulmonary pneumocystosis in an antiretroviral therapy-naïve, HIV-positive patient.

Pneumocystis jirovecii is a common opportunistic fungal pathogen that commonly affects immunocompromised individuals and can cause P. jirovecii pneumonia. Extrapulmonary P. jirovecii infections are extremely rare. Herein, we present a case of an HIV-positive, antiretroviral therapy-naïve patient who had extrapulmonary pneumocystosis (EPC). He presented with complaints of decreased appetite, abdominal fullness, and weight loss. Computed tomography (CT) revealed multiple low-attenuation masses in the spleen, liver, and both adrenal glands but no pulmonary involvement. A core-needle biopsy of a splenic lesion confirmed the diagnosis of EPC. The patient was initiated on intravenous trimethoprim-sulfamethoxazole (TMP-SMX) and CT-guided percutaneous catheter drainage of the splenic lesion was performed. Intravenous TMP-SMX therapy was completed in 3 weeks and intravenous pentamidine (250 mg daily) therapy was commenced. Pentamidine was completed after 3 weeks, and antiretroviral treatment (ART) was initiated with dolutegravir 50 mg and Descovy HT (emtricitabine [200 mg] and tenofovir alafenamide fumarate [25 mg]). After starting ART, the patient's clinical condition improved, and the abscesses gradually reduced. TMP-SMX is commonly used to treat EPC; however, there is no standard method of treatment. ART may become the key to EPC treatment in individuals with HIV infection.

Native valve infective endocarditis due to sequence type 97 community-associated methicillin-resistant Staphylococcus aureus complicated by meningitis and multiple septic emboli in a young healthy adult.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) can cause a wide variety of infections, ranging from skin and soft tissue infections to life-threatening invasive diseases such as necrotizing pneumonia and infective endocarditis. Here, we present a case of a healthy young female presenting with fever, headache and nausea, who was diagnosed with mitral valve infective endocarditis due to CA-MRSA and whose course was complicated by meningitis and multiple septic emboli. The causative MRSA strain belonged to sequence type 97 and harbored SCCmec Ⅳc but not lukS/F-PV genes. ST97, which is frequently isolated from livestock animals and known as a common lineage of livestock-associated MRSA, may cause invasive infection in the community.

Structure and Function of Potential Glycosylation Sites of Dynactin-Associated Protein dynAP.

Overexpression of human dynactin-associated protein (dynAP) transforms NIH3T3 cells. DynAP is a single-pass transmembrane protein with a carboxy-terminal region (amino acids 135-210) exposed to the outside of the cell possessing one potential N-glycosylation site (position 143) and a distal C-terminal region (residues 173-210) harboring a Thr/Ser-rich (T/S) cluster that may be O-glycosylated. In SDS-PAGE, dynAP migrates anomalously at ~ 45 kDa, much larger than expected (22.5 kDa) based on the amino acid composition. Using dynAP mutants, we herein showed that the T/S cluster region is responsible for the anomalous migration. The T/S cluster region is required for transport to the cytoplasmic membrane and cell transformation. We produced and purified the extracellular fragment (dynAP135-210) in secreted form and analyzed the attached glycans. Asn143 displayed complex-type glycosylation, suggesting that oligosaccharide transferase may recognize the NXT/S sequon in the secretory form, but not clearly in full-length dynAP. Core I-type O-glycosylation (Gal-GalNAc) was observed, but the mass spectrometry signal was weak, clearly indicating that further studies are needed to elucidate modifications in this region.

Delayed detection of passive motion in shoulders with a rotator cuff tear.

The aim of this study was to test whether or not the threshold to the detection of passive motion (TTDPM) and passive joint position sense on the affected shoulder of patients with rotator cuff tear (RCT) was impaired compared to those on the unaffected side and to investigate the relationship between the tear size and changes in the TTDPM and passive joint position sense induced by RCT. This study included 21 patients with unilateral RCT before arthroscopic rotator cuff repair. To investigate proprioception in this study, we measured the TTDPM and passive joint position sense in abduction and external rotation using an isokinetic dynamometer. The tear size was evaluated intraoperatively under direct arthroscopic visualization. The TTDPM in abduction and external rotation was significantly longer on the affected side than on the unaffected side. However, the angular absolute error in passive joint position sense in abduction and external rotation was not significantly different between the limbs. A comparison according to the tear size impaired proprioception of the TTDPM in the larger tear group showed significantly longer values than in the smaller group. There was impaired proprioception of TTDPM in patients with RCT, and the impaired proprioception was related to tear severity. Impaired proprioception of TTDPM may inhibit consistent muscle recruitment to achieve precise control. Our results suggest that clinicians should consider proprioceptive exercises for impaired proprioception in their treatment for conservative or postoperative patients.

Effect of formalin fixation on measured concentrations of deposited gadolinium in human tissue: an autopsy study.

BACKGROUND: Generally, studies of gadolinium (Gd) deposition in humans measure concentration by analyzing formalin fixed postmortem tissue. However, the effect of formalin fixation on measured Gd concentration has not been well investigated. PURPOSE: To evaluate the effect of fixation by comparing Gd concentration in fresh versus formalin-fixed postmortem human tissues. MATERIAL AND METHODS: Fresh samples of bone and skin were collected from autopsy cases with previous exposure to Gd-based contrast agents (GBCAs). The type of GBCA administered, dose, and estimated glomerular filtration rate were recorded. Each tissue sample was cut into three aliquots. Paired samples were stored fresh frozen while the remaining two were stored in 10% neutral buffered formalin for one and three months, respectively. Gd concentration was measured using ICP-MS. RESULTS: Of 18 autopsy cases studied, 12 were exposed to only macrocyclic GBCA, one to only linear agents, and five received both macrocyclic and linear agents. On average, Gd concentration for bone decreased 30.7% after one month of fixation (P = 0.043) compared to non-fixed values. There was minimal, if any, change in concentration between one and three months (average decrease 1.5%; P = 0.89). The findings were numerically similar for skin tissue with an average decrease of 36.9% after one month (P = 0.11) and 6.0% (P = 0.73) between one and three months. CONCLUSION: Formalin fixation appears to decrease Gd concentration in bone and skin by approximately 30%-40% on average. The largest decrease occurs within the first 30 days of fixation followed by a considerably smaller decrease at 60 days.

[A Case of Laparoscopic Surgery for Sigmoid Colon Cancer after Cystectomy and Ileal Conduit Construction].

We report a case of laparoscopic sigmoid colon resection for sigmoid colon cancer after cystectomy for bladder cancer and ileal conduit surgery for urinary tract reconstruction. The patient was a male in his 70s. The patient presented to the Department of Gastroenterology with the complaint of nausea and loss of appetite, and findings that were suspicious of intestinal obstruction. The diagnosis was obstructive sigmoid colon cancer. The patient had a history of bladder cancer and had undergone cystectomy and ileal conduit surgery. Intraoperatively, we considered placing a ureteral stent to identify the left ureter through the dorsal mesentery of the sigmoid colon, but we decided that stent placement would be difficult because of a history of conduit stenosis during a previous close examination of a patient with pyelonephritis. On the 21st day, a laparoscopic- assisted sigmoid colon resection was performed. The surgery was completed without any problems such as intraoperative ureteral injury. The patient was discharged home on the 23rd postoperative day. Ten months after the surgery, the patient is alive without recurrence.

Hypercapnia versus normocapnia for emergence from desflurane anaesthesia: Single-blinded randomised controlled study.

BACKGROUND: Rapid emergence from general anaesthesia is desirable only if safety is not sacrificed. Mechanical hyperventilation during hypercapnia produced by carbon dioxide infusion into the inspired gas mixture or by rebreathing was reported to shorten emergence time from inhalation anaesthesia. OBJECTIVES: To test the hypothesis that hypercapnia produced by hypoventilation before desflurane cessation shortens emergence time from general anaesthesia (primary hypothesis) and reduces undesirable cardiorespiratory events. DESIGN: A single-blinded randomised controlled study. SETTING: A single university hospital. PATIENTS: Fifty adult patients undergoing elective abdominal surgery under general anaesthesia using desflurane inhalation and intra-operative epidural anaesthesia. INTERVENTION: The patients were randomly assigned to either the normocapnia or hypercapnia group. MAIN OUTCOME MEASURES: Emergence time from desflurane anaesthesia and comparison of the incidence of 11 predefined undesirable cardiorespiratory events during and after emergence from anaesthesia between the groups. RESULTS: Forty-six patients were included in the analysis. End-tidal carbon dioxide concentrations at cessation of desflurane were 35 ±â€Š6 mmHg (mean ±â€ŠSD) and 52 ±â€Š6 mmHg in normocapnia (n = 23) and hypercapnia groups (n = 23), respectively. Emergence time was significantly faster in the hypercapnia group than the normocapnia group: 9.4 ±â€Š2.4 min, hypercapnia: 5.5 ±â€Š2.6 min, (P < 0.001) with a difference of 3.8 min on average (95% CI: 2.4 to 5.3). Spontaneous breathing established before recovery of consciousness was more evident in hypercapnia patients (normocapnia: 13%, hypercapnia: 96%, P < 0.001). Hypercapnia patients had more episodes of bradypnoea and apnoea before emergence of consciousness. In contrast, after tracheal extubation, incidences of bradypnoea and hypopnoea were more common in the normocapnia group. Undesirable cardiovascular events were not common, and no group differences were observed during emergence and postextubation periods. CONCLUSION: Hypoventilation-induced hypercapnia before desflurane cessation shortens the emergence time without causing additional clinically significant undesirable events. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000020143) https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000023266&language=E.

Comparison of Human Tissue Gadolinium Retention and Elimination between Gadoteridol and Gadobenate.

Background Linear gadolinium-based contrast agents (GBCAs) are known to be retained at higher levels of gadolinium than macro-cyclic GBCAs. However, very little is known regarding their relative elimination rates and retained fraction of injected gadolinium. Purpose To quantify and compare gadolinium retention and elimination rates in human brain tissue, skin, and bone obtained from cadavers exposed to single-agent administration of either gadoteridol (macrocyclic GBCA) or gadobenate dimeglumine (linear GBCA). Materials and Methods Autopsy cases from August 2014 to July 2019 of patients exposed to a single type of GBCA, either gadoteridol or gadobenate dimeglumine, either single or multiple doses, were included. Gadolinium levels in the brain, skin, and bone were analyzed with inductively coupled plasma mass spectrometry. Linear regression was used to compare gadolinium retention between agents and estimate elimination rates of the retained gadolinium using the time between last injection and death. Results Twenty-eight cadavers with gadoteridol exposure and nine with gadobenate dimeglumine exposure were identified (22 men; age range, 19-83 years). The median gadolinium retention of gadobenate dimeglumine was 3.0-6.5 times higher than that of gadoteridol in the brain (P < .02), 4.4 times higher in bone (P = .002), and 2.9 times higher in skin (P = .05). Gadolinium retention in the globus pallidus (GP), dentate nucleus (DN), white matter (WM), bone, and skin decreased with time elapsed from last administration to death in both the gadobenate dimeglumine (GP: -3% per twofold increase in time, P = .69; DN: -2%, P = .83; WM: -20%, P = .01; bone: -22%, P = .07; skin: -47%, P < .001) and gadoteridol (GP: -17%, P = .11; DN: -16%, P = .15; WM: -30%, P < .001; bone: -11%, P = .16; skin: -24%, P = .01) groups (P values for elimination are compared with a null hypothesis of no elimination). Conclusion The linear agent gadobenate dimeglumine retains several-fold higher levels of gadolinium in the brain and bone compared with the macrocyclic agent gadoteridol. Nonzero elimination of retained gadolinium was detected in the white matter and skin for both agents. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Tweedle in this issue.

Expression and cell transformation activity of dynactin-associated protein isoforms.

Overexpression of human dynactin-associated protein isoform a (dynAPa) transforms NIH3T3 cells. DynAPa is a single-pass transmembrane protein with a carboxy-terminal region exposed to the outside of cells. According to the NCBI RefSeq database, there may be two other splicing variants of the encoding gene (dynAPb and c). DynAPa and c differ in some amino-terminal residues (NH2 -MVA in dynAPa and NH2 -MEYQLL in dynAPc). DynAPb has the same amino-terminal residues as dynAPc, but lacks 55 residues in the intracellular region. All three isoforms have the same carboxy-terminal region, including the transmembrane domain. Expression of mRNAs of three splicing variants was found in human cancer cell lines ACHN and Caki-1. The subcellular localization and in vitro cell transformation ability of the three isoforms were examined using NIH3T3 cells overexpressing each respective isoform. All isoforms were found to be localized to the Golgi apparatus and plasma membrane, where the carboxy-terminal region was exposed to the outside of cells. Cell transformation was tested using focus formation due to loss of contact inhibition of cell proliferation, and colony formation was examined on soft agar and spheroid formation in ultralow U-bottomed wells. DynAPa robustly formed foci and colonies on soft agar and spheroid, whereas these abilities were considerably decreased for dynAPb and completely lost in dynAPc. These findings warrant dissection studies to identify the dynAP domain that is required for cell transformation.

Effects of opioids on respiration assessed by a contact-free unconstraint respiratory monitor with load cells under the bed in patients with advanced cancer.

Nocturnal periodic breathing of chronic opioid users has been predominantly documented by the use of polysomnography. No previous studies have assessed the opioid effects of respiratory rhythms throughout the day without the use of physical restraint. We recently developed a contact-free unconstraint vital sign monitoring system with four load cells placed under the bed legs, which allows continuous measurements of respiratory change at the center of gravity on the bed. We aimed to reveal details of the patient's 24-h respiratory status under a monitoring system and to test the hypothesis that respiratory rhythm abnormalities are opioid dose-dependent and worsen during the night time. Continuous 48-h respiratory measurements were successfully performed in 51 patients with advanced cancer (12 opioid-free patients and 39 opioid-receiving patients). Medians of respiratory variables with minimal body movement artifacts were calculated for each 8-h split time period. Compared with opioid-free patients, opioid-receiving patients had slower respiratory rate with higher respiratory rate irregularity without changing tidal centroid shift regardless of the time period. Irregular ataxic breathing was only identified in opioid-receiving patients (33%, P = 0.023) whereas incidence rate of periodic breathing did not differ between the groups. Multivariate regression analyses revealed that opioid dose was an independent risk factor for occurrence of irregular breathing [odds ratio 1.81 (95% CI: 1.39-2.36), P < 0.001], and ataxic breathing [odds ratio 2.08 (95% CI: 1.60-2.71), P < 0.001]. Females developed the ataxic breathing at lower opioid dose compared with males. We conclude that respiratory rhythm irregularity is a predominant specific feature of opioid dose-dependent respiratory depression particularly in female patients with advanced cancer.NEW & NOTEWORTHY Through usage of a novel contact-free unconstraint vital sign monitoring system with four load cells placed under the bed legs allowing continuous measurements of respiratory changes of center of gravity on the bed, this study is the first to assess detailed respiratory characteristics throughout day and night periods without interference of daily activities in patients with advanced cancer receiving opioids. Respiratory rhythm irregularity is a predominant specific feature of opioid dose-dependent respiratory depression particularly in female patients with advanced cancer.