Recovery with a fan-cooling jacket after exposure to high solar radiation during exercise in hot outdoor environments.

The study aimed to investigate the effect of body cooling with a fan-cooling jacket on body temperature responses during recovery after exercise when exposed to high solar radiation in a hot outdoor environment. Nine males cycled using ergometer until their rectal temperature increased to 38.50 °C in hot outdoor environments, followed by body cooling recovery in warm indoor environments. Subjects repeatedly performed the cycling exercise protocol, which consisted of one set of 5 min at a load of 1.5 watt/kg body weight and 15 min at a load of 2.0 watt/kg body weight at 60 rpm. Body cooling recovery consisted of cold water ingestion (10°C: CON) or cold water ingestion + wearing a fan-cooling jacket (FAN) until the rectal temperature decreased to 37.75°C. The time for the rectal temperature to reach 38.5°C did not differ between the two trials. The rate of decrease in rectal temperature at recovery tended to be higher in FAN trial than in CON trial (P = 0.082). The rate of decrease in tympanic temperature was higher in FAN trials than in CON trials (P = 0.002). The rate of decrease in mean skin temperature at the first 20 min of recovery was higher in FAN than in CON trial (P = 0.013). Body cooling recovery with a fan-cooling jacket in addition to cold water ingestion may be effective in reducing elevated tympanic and skin temperatures after exercise in the heat under a clear sky, but may be difficult to decrease rectal temperature.

Deep Learning-based Post Hoc CT Denoising for the Coronary Perivascular Fat Attenuation Index.

RATIONALE AND OBJECTIVES: Coronary inflammation related to high-risk hemorrhagic plaques can be captured by the perivascular fat attenuation index (FAI) using coronary computed tomography angiography (CCTA). Since the FAI is susceptible to image noise, we believe deep learning (DL)-based post hoc noise reduction can improve diagnostic capability. We aimed to assess the diagnostic performance of the FAI in DL-based denoised high-fidelity CCTA images compared with coronary plaque magnetic resonance imaging (MRI) delivered high-intensity hemorrhagic plaques (HIPs). MATERIALS AND METHODS: We retrospectively reviewed 43 patients who underwent CCTA and coronary plaque MRI. We generated high-fidelity CCTA images by denoising the standard CCTA images using a residual dense network that supervised the denoising task by averaging three cardiac phases with nonrigid registration. We measured the FAIs as the mean CT value of all voxels (range of -190 to -30 HU) located within a radial distance from the outer proximal right coronary artery wall. The diagnostic reference standard was defined as HIPs (high-risk hemorrhagic plaques) using MRI. The diagnostic performance of the FAI in the original and denoised images was assessed using receiver operating characteristic curves. RESULTS: Of 43 patients, 13 had HIPs. The denoised CCTA improved the area under the curve (0.89 [95% confidence interval (CI) 0.78-0.99]) of the FAI compared with that in the original image (0.77 [95% CI, 0.62-0.91], p = 0.008). The optimal cutoff value for predicting HIPs in denoised CCTA was -69 HU with 0.85 (11/13) sensitivity, 0.79 (25/30) specificity, and 0.80 (36/43) accuracy. CONCLUSION: DL-based denoised high-fidelity CCTA improved the AUC and specificity of the FAI for predicting HIPs.

Comparison of the effects of high and low levels of solar radiations on exercise capacity in hot outdoor environments.

BACKGROUND: High solar radiation from the sun in the heat outdoor may be impaired exercise capacity. This study aimed to compare the effects of different levels of solar radiation on exercise capacity and evaluate skin temperature responses in the heat. METHODS: Seven male participants performed cycling exercise at 60% of their maximal oxygen uptake until volitional exhaustion in hot outdoor environments (approximately 33-35°C, 40-50% relative humidity) under both clear sky (high solar radiation trial: 1062±50 W/m2) and under thick clouds (low solar radiation trial: 438±52 W/m2). RESULTS: The time to exhaustion of the participants was shorter in the high solar radiation trial (32.0±12.4 min) than in the low solar radiation trial (39.2±18.0 min: P=0.045). Mean skin temperature was significantly higher in the high solar radiation trial than that in the low solar radiation trial (P<0.05); however, the rectal temperature did not differ significantly between the two trials. The high solar radiation trial had narrower core-to-skin temperature gradient, greater the body heat gain from the sun, and higher rating of perceived exertion than the low solar radiation trial. CONCLUSIONS: These results indicate that high solar radiation during outdoor exercise in the heat causes a greater increase in skin temperature and body heat gain from the sun than low solar radiation and consequently impairs exercise capacity.

Pre-cooling with ingesting a high-carbohydrate ice slurry on thermoregulatory responses and subcutaneous interstitial fluid glucose during heat exposure.

The purpose of this study was to compare the effects of ingesting ice slurries with two different carbohydrate contents on body temperatures and the subcutaneous interstitial fluid glucose level during heat exposure. Seven physically active men underwent one of three interventions: the ingestion of 7.5 g/kg of a control beverage (CON: 26°C), a normal-carbohydrate ice slurry (NCIS: -1°C), or a high-carbohydrate ice slurry (HCIS: -5°C). The participants were monitored for a 120-min period that included 10 min of rest, 25 min of exposure to the experimental cooling intervention (during which the beverage was ingested), and 85 min of seated rest in a climate chamber (36°C, 50% relative humidity). The rectal temperature in the HCIS and NCIS trials was lower than that in the CON trial from 40 to 75 min. The infrared tympanic temperature was also lower in the HCIS and NCIS trials than in the CON trial from 20 to 50 min, whereas the deep thigh or mean skin temperatures were not significantly different among the three groups. From 90 to 120 min, the subcutaneous interstitial fluid glucose level in the NCIS trial was lower than that at 65 min; however, reductions were not seen in the HCIS and CON trials. These findings suggest that both HCIS ingestion and conventional NCIS ingestion were effective cooling strategies for reducing thermal strain, while HCIS ingestion may also enable a higher subcutaneous interstitial fluid glucose level to be maintained, ensuring an adequate supply of required muscle substrates.

Herpes zoster in patients with lung cancer treated with PD-1/PD-L1 antibodies.

Background: There are no available clinical data on immunotherapy and the risk of herpes zoster. Materials & methods: This retrospective study included patients with recurrent or advanced lung cancer who were inoperable and ineligible for radiotherapy and were treated with either a PD-1/PD-L1 antibody (136 patients) or an EGFR tyrosine kinase inhibitor (149 patients) at Jichi Medical University Hospital between January 2016 and December 2018. Results: Herpes zoster-free survival was significantly shorter in the PD-1/PD-L1 antibody-treated group compared with the EGFR tyrosine kinase inhibitor-treated group (hazard ratio: 0.20; 95% CI: 0.048-0.84; p = 0.016). PD-1/PD-L1 antibody administration was independently and significantly associated with herpes zoster occurrence. Conclusion: Clinicians should anticipate herpes zoster in patients with lung cancer during treatment with PD-1/PD-L1 antibodies.

There are no available clinical data on immunotherapy and the risk of herpes zoster. This retrospective study included patients with recurrent or advanced lung cancer who were inoperable and ineligible for radiotherapy and were treated with either an immune checkpoint inhibitor (136 patients) or an EGFR tyrosine kinase inhibitor (149 patients) through the authors' university between January 2016 and December 2018. The herpes zoster-free period was significantly shorter in the immune checkpoint inhibitor-treated group compared with the EGFR tyrosine kinase inhibitor-treated group (hazard ratio: 0.20; 95% CI: 0.048­0.84; p = 0.016). Immune checkpoint inhibitor antibody administration was independently and significantly associated with herpes zoster occurrence. Clinicians should be cautious of herpes zoster in patients with lung cancer during treatment with immune checkpoint inhibitors.

Case Report: Countermeasures Against Heat and Coronavirus for Japanese Athletes at the Tokyo 2020 Olympics and Paralympic Games.

The Tokyo 2020 Olympics and Paralympic Games were held in the hottest environment in the history of the games. Additionally, the worldwide coronavirus disease 2019 (COVID-19) pandemic necessitated daily polymerase chain reaction (PCR) testing during the games, wearing a mask became mandatory publicly, and it was an unheard and unique Olympic with no spectators. Heat acclimation, hydration, and body cooling are essential for safe and high-performance activities in hot environments. In 2015, the Japan Institute of Sports Sciences launched the "Heat Countermeasure Project" to conduct experiments and practical research on heat countermeasures and investigate issues related to heat countermeasures in each athletic event. The results obtained were proposed to various Japan national sports teams, and support for heat countermeasures for the Tokyo 2020 games was promoted in consultation with national federations. Furthermore, due to the COVID-19 pandemic, infectious disease countermeasures for the Tokyo 2020 Games during support were a must. Moreover, athletes, coaches, and team staff could not avoid implementing heat countermeasures while adopting measures against infectious diseases. This study aimed to clarify the issues faced with heat countermeasures and report on heat acclimation training and cooling support efforts, considering measures against infectious diseases.

Virulent Pseudomonas aeruginosa pneumonia in an immunocompetent adult associated with a home whirlpool bath: A case report.

We present a case of life-threatening pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa) in a healthy 67-year-old man. Rapid disseminated infection resulted in the right hemorrhagic pneumonia and bacteremia. Antimicrobial therapy had limited effects, radical pneumonectomy eventually resolved the prolonged infection. Concurrently, we explored the environmental factors responsible for fulminant P. aeruginosa infection. Multi-locus sequence typing demonstrated that P. aeruginosa isolated from the patient was identical to that collected from home whirlpool bath by the common virulent factor gene. Massive inhalation of contaminated aerosol and pathogen virulence may have synergistically contributed to the severity in this case.

TYRO3 Knockdown Suppresses the Growth of Myeloid Leukaemia Cells.

BACKGROUND/AIM: TYRO3 is a member of the TAM family (TYRO3, AXL, and MERTK) of receptor tyrosine kinases. While the roles of activated AXL and MERTK in the growth of leukaemia cells have been reported, the effect of TYRO3 has not been determined. Therefore, we examined the effects of TYRO3 knockdown on the growth of leukaemia cell lines. MATERIALS AND METHODS: Three human leukaemia cell lines (AA derived from pure erythroid leukaemia, OCI/AML2, and K562), which express TYRO3 protein were used in this study. To induce TYRO3 knockdown, small interfering RNA (siRNA) against TYRO3 was transfected using an electroporation system. Cell growth was assessed by a colorimetric assay. The expression levels and activation of various signalling proteins were examined by immunoblotting. Changes in comprehensive gene expression after TYRO3 knockdown were examined by microarray analysis. RESULTS: TYRO3 knockdown suppressed cell growth in the leukaemia cell lines tested. Additionally, the knockdown suppressed phosphorylation of signal transducer and activator of transcription-3 in AA cells, and extracellular signal-regulated kinase (ERK) 1/2 in AA and OCI/AML2 cells; both are downstream molecules of TYRO3 signalling. TYRO3 knockdown also suppressed the expression of survivin in all the cell lines. TYRO3 knockdown potently suppressed TYRO3 mRNA expression but not that of AXL and MERTK. Furthermore, TYRO3 knockdown suppressed cyclin D1 mRNA expression, which is a downstream molecule of ERK. CONCLUSION: TYRO3 plays a role in leukaemia cell growth and is a potential therapeutic target for leukaemia.

Mild hyperbaric oxygen for the early improvement of mood disturbance induced by high-intensity exercise.

BACKGROUND: Excessive training stress can result in decreased performance and deep fatigue due to hormonal changes. There are few available data on recovery methods for mood disturbance, especially fatigue, after high-intensity training. This study, therefore, aimed to examine the effects of mild hyperbaric oxygen at 1.3 atmospheres absolute with 31% oxygen on mood disturbance induced by high-intensity exercises. METHODS: Ten healthy adult men participated in and completed 2 trials: the control (CON) trial and the mild hyperbaric oxygen (MHO) trial. In a randomized crossover design, each subject cycled for 60 min at the physical work capacity at 75% of their maximal heart rate and were subsequently exposed to the CON and MHO conditions for 60 min as the recovery period. RESULTS: During the 20 to 40 min recovery time points, the average change ratio of heart rates was lower in the MHO trial than in CON (P<0.05). We observed that the fatigue-inertia, tension-anxiety, and total mood disturbance Profile of Mood States (POMS) scores decreased 60 min post-exercise in the MHO trial, but no differences of these scores were observed in the CON trial. There were no differences in oxidative stress, derived-reactive oxygen metabolites, and biological antioxidant potential between both trials. These results suggest that impaired mood states induced by high-intensity exercise can be improved early by MHO without any changes in oxidative stress. This improvement may be associated with decreased heart rate secondary to MHO exposure after the high intensity exercise. CONCLUSIONS: We conclude that MHO can improve mood disturbances, especially in the fatigue-inertia and tension-anxiety domains, after high-intensity exercise. This study suggest that MHO is potentially an effective recovery method for mood states after high-intensity training.

A clinical survey of dehydration during winter training in elite fencing athletes.

BACKGROUND: Fencing is suggested as one of the most dangerous sporting events in terms of dehydration because of the uniform and gear covering the entire body. We aimed to elucidate the change in hydration status before and after training in elite fencing athletes in winter along with the assessment of sex and fencing style differences. METHODS: Twenty-seven elite fencing athletes (14 males and 13 females) belonging to the Japanese National Team participated in this clinical survey. Dehydration status before and after winter training was assessed using body mass change, fluid intake, urine osmolarity, urine specific gravity (USG), and sodium, potassium, chlorine, and creatinine levels. RESULTS: More than half of the participants (59.3%) drank water and tea during training. The change rate of body mass (males vs. females, 1.61±0.82% vs. 0.45±0.68%, P<0.01; foil vs. epee, 2.25±0.45% vs. 1.16±0.72%, P<0.05) and sweating rate (males vs. females, 938±251 g/h vs. 506±92 g/h, P<0.01; foil vs. epee, 1136±156 g/h vs. 796±207 g/h, P<0.05) during training showed significant differences between sexes and fencing styles. Of all participants, 66.7% were dehydrated (USG≥1.020), and 37.0% were seriously dehydrated (USG≥1.030) before training. CONCLUSIONS: Fencing athletes may be susceptible to severe dehydration before training, even in winter. Additionally, males and foil fencers appear to be at a greater risk than females and epee fencers of developing dehydration during exercise.

Differences of body composition and physical strength among Japanese and Thai older adults living in Chiang Mai, Thailand: an inter-ethnic cross-sectional study.

BACKGROUND: The number of adults aged over 65 years is rapidly increasing in several Southeast Asian countries. Muscle mass decreases with age, leading to sarcopenia. The primary objective of this study was to determine whether differences exist in the body composition and physical strength, according to ethnicity, among community-dwelling Japanese and Thai older adults living in Chiang Mai Province, Thailand. METHODS: A survey was conducted in February and March 2019. Japanese and Thai adults aged ≥ 60 years living in Chiang Mai Province were recruited through community clubs. Participants completed a self-administered questionnaire that enabled collection of data on age, sex, educational background, marital status, annual income, current medical conditions, smoking and alcohol consumption, and exercise habits. Measurements were collected on height, weight, body composition, blood pressure, hand grip, and walking speed for 6 m. Body composition was measured using a standing-posture 8-electrode multifrequency bioimpedance analysis analyzer. Hand grip of each hand was measured with the patient in the standing position using a digital grip dynamometer. Multivariable logistic regression was used to determine factors associated with skeletal muscle mass index (SMI). RESULTS: Of the total 119 participants, 47 were Japanese (26 men, 21 women) and 72 were Thai (16 men, 56 women). The prevalence of a low SMI was 3/26 (12%), 1/21 (5%), 6/16 (38%), and 5/56 (9%) among Japanese men, Japanese women, Thai men, and Thai women, respectively. The prevalence of low muscle strength was 2/26 (8%), 2/21 (10%), 3/16 (19%), and 13/56 (23%) among Japanese men, Japanese women, Thai men, and Thai women, respectively. There were significant differences between ethnic groups in body mass index for both sexes, percentage body fat in women, SMI in men, and average grip strength in men. Ethnic group, sex, age, and body mass index were independent predictors of SMI. CONCLUSIONS: Ethnicity had a clinically important effect on body composition and physical strength among older Japanese and Thai adults living in a similar environment.

On-site environmental DNA detection of species using ultrarapid mobile PCR.

Molecular methods, including those for environmental DNA (eDNA), provide essential information for biological and conservation sciences. Molecular measurements are often performed in the laboratory, which limits their scope, especially for rapid on-site analysis. eDNA methods for species detection provide essential information for the management and conservation of species and communities in various environments. We have developed an innovative novel method for on-site eDNA measurements using an ultrarapid mobile PCR platform. We tested the ability of our method to detect the distribution of silver carp, Hypophthalmichthys molitrix, in rivers and lakes. Our method reduced the measurement time to 30 min and provided high detectability of aquatic organisms compared to national observation surveys that use multiple fishing nets and laboratory extraction/detection using a benchtop qPCR platform. Our on-site eDNA method can be immediately applied to various taxa and environments.

Suprabasin-derived bioactive peptides identified by plasma peptidomics.

Identification of low-abundance, low-molecular-weight native peptides using non-tryptic plasma has long remained an unmet challenge, leaving potential bioactive/biomarker peptides undiscovered. We have succeeded in efficiently removing high-abundance plasma proteins to enrich and comprehensively identify low-molecular-weight native peptides using mass spectrometry. Native peptide sequences were chemically synthesized and subsequent functional analyses resulted in the discovery of three novel bioactive polypeptides derived from an epidermal differentiation marker protein, suprabasin. SBSN_HUMAN[279-295] potently suppressed food/water intake and induced locomotor activity when injected intraperitoneally, while SBSN_HUMAN[225-237] and SBSN_HUMAN[243-259] stimulated the expression of proinflammatory cytokines via activation of NF-κB signaling in vascular cells. SBSN_HUMAN[225-237] and SBSN_HUMAN[279-295] immunoreactivities were present in almost all human organs analyzed, while immunoreactive SBSN_HUMAN[243-259] was abundant in the liver and pancreas. Human macrophages expressed the three suprabasin-derived peptides. This study illustrates a new approach for discovering unknown bioactive peptides in plasma via the generation of peptide libraries using a novel peptidomic strategy.

Can Muscle Mass Be Maintained with A Simple Resistance Intervention in the Older People? A Cluster Randomized Controlled Trial in Thailand.

The aging population is rapidly increasing worldwide. Sarcopenia is a common and important health problem among older people. The prevalence of sarcopenia among older Thai adults is increasing. Exercise intervention for sarcopenia prevention may significantly improve muscle strength, body balance, and muscle mass. Therefore, this study aimed to investigate the effects of a simple resistance intervention (SRI) program in preventing sarcopenia on physiological outcomes among community-dwelling older Thai adults. This study was a 12-week randomized controlled trial, which included 80 community-dwelling older adults in Chiang Mai, Thailand, who were randomly assigned into control (40 participants who performed usual exercise) and intervention (40 participants who performed the SRI program) groups. The SRI program was a home-based program consisting of 30 min of resistance exercise three times/week for 12 weeks, health education on sarcopenia. After 12 weeks, all physiological outcomes were measured and were significantly improved in the intervention group compared with baseline; hand grip, skeletal muscle mass index, and walking speed were significantly improved in the intervention group compared with the control group. Based on our results, the SRI program may prevent muscle weakness in community-dwelling older people in Thailand.

Early Pathological JC Virus Lesions in a Patient without Any MRI-based Indications.

A 70-year-old woman with a human T-cell leukemia virus type 1 infection without any focal neurological symptoms showed age-related atherosclerotic changes in the white matter without any suspicious signal changes suggestive of progressive multifocal leukoencephalopathy (PML) based on the findings of MRI. Viral polymerase chain reaction (PCR) revealed 6,700 copies/mL of the JC virus genome in the cerebrospinal fluid (CSF). An immuno-pathological examination of the autopsied brain revealed JC virus capsid proteins, and in situ hybridization confirmed a JC virus infection, indicating that an active infection begins at the radiologically indistinguishable phase of PML. An early JC virus infection is probably associated with small, scattered demyelinating lesions around the cortico-medullary area of the cortex.

Maggot debridement therapy in critical limb ischaemia: a case study.

OBJECTIVE: In critical limb ischaemia (CLI), first-line therapy is revascularisation, but alternative treatment options are needed in certain cases. Maggot debridement therapy (MDT) is historically considered to be contraindicated in ischaemic ulcers. Wound care in patients with CLI is becoming increasingly diverse with the development of novel revascularisation strategies; therefore, CLI now needs to be reconsidered as an indication for MDT. METHOD: We retrospectively reviewed five legs with CLI (five male, one female) treated with MDT between January 2013 and December 2017. Changes in skin perfusion pressure (SPP) around the ulcer before and after MDT were evaluated. One or two cycles of MDT were performed (eight in total). We also evaluated the proportion of necrotic tissue in the ulcer and the presence of exposed necrotic bone. The proportion of necrotic tissue in the ulcer was classified as NT 1+ (<25%), NT 2+ (25-50%), NT 3+ (50-75%) or NT 4+ (>75%). RESULTS: When the proportion of necrotic tissue was >50%, with no exposed necrotic bone in the wound, an increase in SPP was observed after five (62.5%) of eight cycles of MDT. And with a proportion of necrotic tissue of <25% and/or exposed necrotic bone in the wound, a decrease in SPP was observed after three (37.5%) of eight cycles. Wound healing was accelerated in the presence of increased SPP. CONCLUSION: Effective MDT with increased SPP requires an ulcerative state of necrotic tissue grade > NT 3+, with no exposed necrotic bone.

Water-in-CO2 Microemulsions Stabilized by an Efficient Catanionic Surfactant.

To facilitate potential applications of water-in-supercritical CO2 microemulsions (W/CO2 µEs) efficient and environmentally responsible surfactants are required with low levels of fluorination. As well as being able to stabilize water-CO2 interfaces, these surfactants must also be economical, prevent bioaccumulation and strong adhesion, deactivation of enzymes, and be tolerant to high salt environments. Recently, an ion paired catanionic surfactant with environmentally acceptable fluorinated C6 tails was found to be very effective at stabilizing W/CO2 µEs with high water-to-surfactant molar ratios (W0) up to ∼50 (Sagisaka, M.; et al. Langmuir 2019, 35, 3445-3454). As the cationic and anionic constituent surfactants alone did not stabilize W/CO2 µEs, this was the first demonstration of surfactant synergistic effects in W/CO2 microemulsions. The aim of this new study is to understand the origin of these intriguing effects by detailed investigations of nanostructure in W/CO2 microemulsions using high-pressure small-angle neutron scattering (HP-SANS). These HP-SANS experiments have been used to determine the headgroup interfacial area and volume, aggregation number, and effective packing parameter (EPP). These SANS data suggest the effectiveness of this surfactant originates from increased EPP and decreased hydrophilic/CO2-philic balance, related to a reduced effective headgroup ionicity. This surfactant bears separate C6F13 tails and oppositely charged headgroups, and was found to have a EPP value similar to that of a double C4F9-tail anionic surfactant (4FG(EO)2), which was previously reported to be one of most efficient stabilizers for W/CO2 µEs (maximum W0 = 60-80). Catanionic surfactants based on this new design will be key for generating superefficient W/CO2 µEs with high stability and water solubilization.

Metformin suppresses the growth of leukemia cells partly through downregulation of AXL receptor tyrosine kinase.

Metformin is an anti-diabetic drug known to have anticancer activity by inhibiting mechanistic target of rapamycin (mTOR); however, other molecular mechanisms may also be involved. In this study, we examined the effects of metformin on the activity of receptor tyrosine kinases of the TAM (TYRO3, AXL, and MERTK) family, which have important roles in leukemia cell growth. The results indicated that metformin suppressed the in vitro growth of four leukemia cell lines, OCI/AML2, OCI/AML3, THP-1, and K562, in a dose-dependent manner, which corresponded to the downregulation of the expression and phosphorylation of AXL and inhibition of its downstream targets such as phosphorylation of STAT3. Furthermore, metformin augmented the suppressive effects of a small-molecule AXL inhibitor TP-0903 on the growth of OCI/AML3 and K562 cells and prevented doxorubicin-induced AXL activation in K562 cells, which induces chemoresistance in leukemia cells, thus potentiating doxorubicin anti-proliferative effects. Given that metformin also downregulated expression of TYRO3 and phosphorylation of MERTK, these findings indicate that anti-leukemic effects exerted by metformin could be partly due to the inhibition of TAM kinases. Thus, metformin has a clinical potential for patients with leukemia cells positive for AXL and the other TAM proteins as well as activated mTOR.

Salmonella enterica Subspecies arizonae Detected from Bilateral Pleural Fluid in a Patient with Systemic Lupus Erythematosus and Malignant Lymphoma.

A 72-year-old woman was admitted to our hospital with bilateral pleural effusions. She had a 31-year history of systemic lupus erythematosus and had been treated with prednisolone and azathioprine. Pleural fluid culture revealed Salmonella enterica subsp. arizonae infection. This pathogen rarely infects humans but is commonly found in the gut flora of reptiles, especially snakes. Our patient had not come in contact with reptiles. Despite antibiotic therapies and negative pleural cultures, the pleural effusion persisted. Colon cancer was detected concomitantly, and she finally died. The autopsy revealed that the pleuritis was due to underlying diffuse large B cell lymphoma.

Hypoxia Up-regulates HIF Expression While Suppressing Cell Growth and NOTCH Activity in Leukaemia Cells.

AIM: To examine the influence of hypoxia on the in vitro growth of leukaemia cells and the activity of signalling proteins to better understand the pathophysiology of leukaemia cells in human bone marrow. MATERIALS AND METHODS: Six human leukaemia cell lines were cultured under normoxic or hypoxic conditions. Cell growth, recovery of clonogenic cells, and the expression and activation of various signalling proteins were examined. RESULTS: Hypoxia suppressed cell growth and the recovery of clonogenic cells. Moreover, hypoxia up-regulated hypoxia-inducible factor (HIF) 1α and HIF2α expression while suppressing the expression and activation of NOTCH1, mechanistic target of rapamycin kinase (mTOR) activation, and nuclear factor-kappa B (NF-κB) phosphorylation. CONCLUSION: We found that hypoxia up-regulated HIF expression while it suppressed the self-renewal capacity of leukaemia cells, NOTCH activity, and expression of its down-stream signalling molecules, which differs from previous reports mentioning that HIF activates NOTCH signalling. Our findings serve to further elucidate the in vivo pathophysiology of leukaemia cells.