Septic shock caused by a carbon dioxide-dependent and extended spectrum ß-lactamase-producing Proteus mirabilis small colony variant in a long-term bedridden patient.

Here, we report a 60-year-old chronically bedridden man with cerebral palsy who had septic shock following a history of urinary tract infection with extended spectrum ß-lactamase-producing and auxotrophic Proteus mirabilis detected on blood and urine cultures. This auxotroph formed small colonies only on the blood agar at 24 h in 5% CO2, but not in the conditions without CO2, and lacked motility and some biochemical activities. The five-year history of stones in the right renal pelvis suggests chronic urinary tract infection with P. mirabilis requiring a 28-day antibiotic treatment. This paper highlights that the CO2-dependent P. mirabilis small colony variant may cause sepsis, probably due to chronic infection in uroliths, which should warrant immediate identification.

Association of patient satisfaction with direct oral anticoagulants and the clinical outcomes: Findings from the SAKURA AF registry.

BACKGROUND: The burden or benefit of anticoagulation treatment affects patient satisfaction, which may in turn affect the adherence to the treatment and subsequent outcomes. Thus, we hypothesized that the patient satisfaction with direct oral anticoagulants (DOACs) may influence the clinical outcome in patients with atrial fibrillation (AF). METHODS AND RESULTS: We investigated the clinical outcomes among 719 DOAC users (age 71.9 ± 9.1 years, 184 females, and 449 persistent AF) enrolled in the SAKURA AF Registry who completed a satisfaction questionnaire with anticoagulation therapy by means of the Anti-Clot Treatment Scale (ACTS), which included 12-item burden and 3-item benefit scales. During a 41.8-month-follow-up, a stroke/systemic embolism (SE) occurred in 27 patients (3.8%) and major bleeding events in 25 (3.5%). A univariate Cox regression analysis revealed that an older age, persistent AF, higher CHA2DS2-VASc score, no history of AF ablation, lower creatinine clearance, and lower ACTS benefit scores were significantly associated with an increased risk of a stroke/SE, but not with major bleeding events. A low benefit score remained an independent predictor of a stroke/SE even after a multivariate adjustment. The ACTS burden scores were not associated with any clinical events. CONCLUSIONS: We found a strong association between a low benefit satisfaction and increased stroke risk. We should follow patients carefully to educate them on treatment importance for patients unsatisfied with the benefits of DOACs for stroke prevention.

[A Case of Metastatic Colorectal Cancer with Hyperammonemic Encephalopathy Induced by mFOLFOX6 and SOX Therapy].

A 77-year-old man was given a diagnosis of pT4aN0M1a(PUL2), stage Ⅳ, RAS mutant type, after the operation for advanced ascending colon cancer. He was administered mFOLFOX6 plus Bmab as first-line chemotherapy. He showed consciousness disturbance on the 2nd day during the 6 cycles. Because of head computed tomography and magnetic resonance imaging showing no abnormal findings, we diagnosed convulsive seizure. His consciousness level gradually improved after intravenous infusion. He showed consciousness disturbance on the 2nd day during the 7 cycles again. Because blood ammonia level were high at 400µg/dL, he was diagnosed as hyperammonemic encephalopathy. His consciousness level rapidly recovered after branched chain amino acid(BCAA)infusion. SOX plus Bmab therapy was started as a post-treatment, he developed hyperammonemia(NH3 288µg/dL)again, on the 4th day during the 3 cycles. After taking of oral administration of BCAA and lactulose, the recurrence of hyperammonemic encephalopathy was not found. Therefore, 3 cycles of SOX plus Bmab therapy and 12 cycles of IRIS plus Bmab therapy were administered.

Maintenance antisepsis in reducing the rate of late-onset central venous catheter-related bloodstream infection: A comparison of 0.05% and 1% chlorhexidine.

BACKGROUND: Bundled measures have been recommended to reduce the risk of central venous catheter (CVC)-related bloodstream infection. However, the importance of each procedure involved in CVC insertion/management for preventing catheter-related bloodstream infection (CRBSI) has not been thoroughly assessed. We aimed to analyze the effectiveness of maintenance antisepsis at the CVC insertion site in reducing the CRBSI risk through comparing the use of 0.05% chlorhexidine to 1% chlorhexidine. PATIENTS AND METHODS: In the South Miyagi Medical Center, Japan, 372 patients with a CVC who had undergone antisepsis maintenance using 0.05% chlorhexidine swabs 12 months prior to implementing 1% chlorhexidine swabs, and 344 patients at 12 months post-implementation of 1% chlorhexidine swabs, were followed prospectively for the development of CRBSI and signs of infection, and their data compared. RESULTS: Post-implementation of the 1% chlorhexidine swabs, the CRBSI rate decreased from 3.64/1000 catheter-days to 1.77/1000 catheter-days. The risk of CRBSI decreased to 0.465 (95% confidence interval [CI]: 0.216-1.001). Furthermore, the risk of CRBSI ≥20 days after CVC insertion decreased to 0.200 (95% CI: 0.049-0.867); however, we found no difference between 0.05% and 1% chlorhexidine use within 19 days of CVC insertion. The increased number of patients with insertion site tenderness after implementing 1% chlorhexidine indicated a possible adverse effect of chlorhexidine. CONCLUSION: Maintenance antisepsis with 1% chlorhexidine decreased the risk of developing CRBSI ≥20 days after CVC insertion, indicating the effectiveness of antisepsis with 1% chlorhexidine. Our data highlight the importance of maintenance antisepsis in reducing the rate of late-phase CRBSI.

Patient Satisfaction with Direct Oral Anticoagulants and Warfarin.

The burden of anticoagulation treatment affects patient satisfaction, which in turn affects adherence to treatment. Thus, we must thoroughly understand the advantages of direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs)/warfarin given for stroke prevention in patients with atrial fibrillation (AF). We compared satisfaction with anticoagulation therapy between 654 DOAC and 821 warfarin users enrolled in the SAKURA AF Registry. Satisfaction was assessed by means of the Anti-Clot Treatment Scale (ACTS), which includes 12-item burdens and 3-item benefits scales, and the treatment satisfaction questionnaire for medication II (TSQM II), which includes 2-item effectiveness, 3-item side effects, 3-item convenience, and 2-item global satisfaction domains. There were no significant between-group differences in TSQM II convenience (67.6 ± 14.5 versus 68.9 ± 14.5, P = 0.280), effectiveness (65.0 ± 13.3 versus 66.0 ± 15.0, P = 0.422), side effects (93.6 ± 13.7 versus 92.8 ± 14.4, P = 0.067), and global satisfaction (64.7 ± 14.9 versus 66.0 ± 14.6, P = 0.407) scores. In contrast, although there was no significant between-group difference in the ACTS benefits scores (9.8 ± 3.1 versus 10.1 ± 3.2, P = 0.051), the ACTS burdens scores (54.5 ± 6.3 versus 52.7 ± 6.9, P < 0.0001) were significantly higher in the DOAC users, independent of age, sex, and DOAC type. We can expect greater burden satisfaction with anticoagulation treatment in patients given a DOAC versus VKA/warfarin. The reduced burden of treatment will translate to greater patient adherence to their treatment plans and a positive effect on clinical outcomes.

[A Case of Gallbladder Carcinoma Producing Alpha-Fetoprotein(AFP)with Metastatic Liver Tumor].

Gallbladder carcinoma producing alpha-fetoprotein(AFP)is rare.We report a case of AFP producing carcinoma of the gallbladder with huge metastatic hepatic tumor.A 81-year-old female with a hepatitis B virus(HBV)had a fever and right hypochondralgia.Abdominal CT showed an enlarged gallbladder with gallbladder stones, a huge tumor in the right lobe of liver, and swelling paraaortic lymph nodes.Acute cholecystitis was treated by percutaneous transhepatic gallbladder drainage (PTGBD).The hepatic tumor was diagnosed as hepatocellular carcinoma for HBV carrier and the high level of AFP and PIVKA- II .We performed right lobectomy, cholecystectomy and the resection of paraaortic lymph nodes.In the resected gallbladder, the papillary tumor was detected.Histopathological diagnosis was moderately to poorly differentiated adenocarcinoma of the gallbladder.The liver tumor and paraaortic lymph nodes were metastases of the gallbladder carcinoma.The both of gallbladder and liver tumor immunohistochemically stained positive to AFP.It was difficult to diagnose the hepatic tumor because of HBV carrier, the high level of AFP and the unnoticed gallbladder tumor.Gallbladder carcinoma with the high level of AFP might have relation to liver metastases.

Sleep restores behavioral plasticity to Drosophila mutants.

Given the role that sleep plays in modulating plasticity, we hypothesized that increasing sleep would restore memory to canonical memory mutants without specifically rescuing the causal molecular lesion. Sleep was increased using three independent strategies: activating the dorsal fan-shaped body, increasing the expression of Fatty acid binding protein (dFabp), or by administering the GABA-A agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP). Short-term memory (STM) or long-term memory (LTM) was evaluated in rutabaga (rut) and dunce (dnc) mutants using aversive phototaxic suppression and courtship conditioning. Each of the three independent strategies increased sleep and restored memory to rut and dnc mutants. Importantly, inducing sleep also reverses memory defects in a Drosophila model of Alzheimer's disease. Together, these data demonstrate that sleep plays a more fundamental role in modulating behavioral plasticity than previously appreciated and suggest that increasing sleep may benefit patients with certain neurological disorders.

Proteinaceous toxins from three species of scorpaeniform fish (lionfish Pterois lunulata, devil stinger Inimicus japonicus and waspfish Hypodytes rubripinnis): close similarity in properties and primary structures to stonefish toxins.

The crude toxins from three species of venomous fish (lionfish Pterois lunulata, devil stinger Inimicus japonicus and waspfish Hypodytes rubripinnis) belonging to the order Scorpaeniformes exhibited mouse-lethal, hemolytic, edema-forming and nociceptive activities. In view of the antigenic cross-reactivity with the stonefish toxins, the primary structures of the stonefish toxin-like toxins from the three scorpaeniform fish were determined by cDNA cloning using primers designed from the highly conserved sequences of the stonefish toxins. Based on the data obtained in gel filtration, immunoblotting and cDNA cloning, each toxin was judged to be a 160 kDa heterodimer composed of 80 kDa α- and ß-subunits. The three scorpaeniform fish toxins contain a B30.2/SPRY domain (∼200 amino acid residues) in the C-terminal region of each subunit, as reported for the toxins from two species of lionfish and two species of stonefish. With respect to the amino acid sequence similarity, the scorpaeniform fish toxins are divided into the following two groups: toxins from three species of lionfish and those from devil stinger, two species of stonefish and waspfish. The phylogenetic tree generated also clearly supports the classification of the toxins.

Increased prevalence of high anti-Cladosporium antibody titers in interstitial lung diseases.

Interstitial lung diseases (ILDs) represent a large group of different diseases, with a large part comprising idiopathic interstitial pneumonias. Differentiating hypersensitivity pneumonitis (HP), especially its chronic form and other ILDs, is difficult because of similarities in radiological manifestation and clinical course, and the difficulty of identifying causative antigens. We recently experienced a patient with Cladosporium-induced chronic HP that developed in a household environment, but the cause had been misdiagnosed as idiopathic interstitial pneumonia for several years. This case highlighted the need for measures differentiating HP from idiopathic interstitial pneumonia. In this study, we examined fungal exposure in ILDs using an antibody titer in serum to identify possible fungus-related HP. We measured the antibody titer to Cladosporium spp. in 34 patients with various ILDs, 17 patients with bronchial asthma, and 21 control subjects using an immunofluorescence assay. ILDs included HP (5 patients), idiopathic interstitial pneumonias (21 patients), and ILDs with collagen vascular diseases (8 patients). Results showed a significantly higher tendency for high anti-Cladosporium antibody titers in ILD groups (12 patients out of 34 patients), compared to patients with bronchial asthma (0/17) or control subjects (0/21). This increase in antibody titers was observed not only in patients with HP, but also in those with idiopathic interstitial pneumonias and those exhibiting collagen vascular diseases with ILDs. This report highlights the pathogenic role of fungal antigens in various ILDs. In conclusion, fungi commonly observed in our living environment such as Cladosporium could be involved in the development of ILDs.

Foraging alters resilience/vulnerability to sleep disruption and starvation in Drosophila.

Recent human studies suggest that genetic polymorphisms allow an individual to maintain optimal cognitive functioning during sleep deprivation. If such polymorphisms were not associated with additional costs, selective pressures would allow these alleles to spread through the population such that an evolutionary alternative to sleep would emerge. To determine whether there are indeed costs associated with resiliency to sleep loss, we challenged natural allelic variants of the foraging gene (for) with either sleep deprivation or starvation. Flies with high levels of Protein Kinase G (PKG) (for(R)) do not display deficits in short-term memory following 12 h of sleep deprivation. However, short-term memory is significantly disrupted when for(R) flies are starved overnight. In contrast, flies with low levels of PKG (for(s), for(s2)) show substantial deficits in short-term memory following sleep deprivation but retain their ability to learn after 12 h of starvation. We found that for(R) phenotypes could be largely recapitulated in for(s) flies by selectively increasing the level of PKG in the α/ß lobes of the mushroom bodies, a structure known to regulate both sleep and memory. Together, these data indicate that whereas the expression of for may appear to provide resilience in one environmental context, it may confer an unexpected vulnerability in other situations. Understanding how these tradeoffs confer resilience or vulnerability to specific environmental challenges may provide additional clues as to why an evolutionary alternative to sleep has not emerged.

Combined Legionella and Escherichia coli lung infection after a tsunami disaster.

Pulmonary infection after a tsunami is often polymicrobial and tends to form chronic pyogenic lung disease, necrotizing pneumonia, and empyemas. We report a combined pulmonary infection of Legionella and multiple antibiotic-resistant Escherichia coli in a previously well 75-year-old woman following immersion in tsunami waters 1 km inland from the Pacific coastline following the Tohoku Region Pacific Coast Earthquake of 2011. She needed drainage several times and the long-term use of multiple antibiotics according to the type of bacteria found and antibiotic susceptibility. We should be mindful of infections caused by multiple pathogens in the environment in Japan as a consequence of a tsunami disaster.

Inducing sleep by remote control facilitates memory consolidation in Drosophila.

Sleep is believed to play an important role in memory consolidation. We induced sleep on demand by expressing the temperature-gated nonspecific cation channel Transient receptor potential cation channel (UAS-TrpA1) in neurons, including those with projections to the dorsal fan-shaped body (FB). When the temperature was raised to 31°C, flies entered a quiescent state that meets the criteria for identifying sleep. When sleep was induced for 4 hours after a massed-training protocol for courtship conditioning that is not capable of inducing long-term memory (LTM) by itself, flies develop an LTM. Activating the dorsal FB in the absence of sleep did not result in the formation of LTM after massed training.

Notch signaling modulates sleep homeostasis and learning after sleep deprivation in Drosophila.

The role of the transmembrane receptor Notch in the adult brain is poorly understood. Here, we provide evidence that bunched, a negative regulator of Notch, is involved in sleep homeostasis. Genetic evidence indicates that interfering with bunched activity in the mushroom bodies (MBs) abolishes sleep homeostasis. Combining bunched and Delta loss-of-function mutations rescues normal homeostasis, suggesting that Notch signaling may be involved in regulating sensitivity to sleep loss. Preventing the downregulation of Delta by overexpressing a wild-type transgene in MBs reduces sleep homeostasis and, importantly, prevents learning impairments induced by sleep deprivation. Similar resistance to sleep loss is observed with Notch(spl-1) gain-of-function mutants. Immunohistochemistry reveals that the Notch receptor is expressed in glia, whereas Delta is localized in neurons. Importantly, the expression in glia of the intracellular domain of Notch, a dominant activated form of the receptor, is sufficient to prevent learning deficits after sleep deprivation. Together, these results identify a novel neuron-glia signaling pathway dependent on Notch and regulated by bunched. These data highlight the emerging role of neuron-glia interactions in regulating both sleep and learning impairments associated with sleep loss.

Sleep deprivation during early-adult development results in long-lasting learning deficits in adult Drosophila.

STUDY OBJECTIVES: Multiple lines of evidence indicate that sleep is important for the developing brain, although little is known about which cellular and molecular pathways are affected. Thus, the aim of this study was to determine whether the early adult life of Drosophila, which is associated with high amounts of sleep and critical periods of brain plasticity, could be used as a model to identify developmental processes that require sleep. SUBJECTS: Wild type Canton-S Drosophila melanogaster. DESIGN; INTERVENTION: Flies were sleep deprived on their first full day of adult life and allowed to recover undisturbed for at least 3 days. The animals were then tested for short-term memory and response-inhibition using aversive phototaxis suppression (APS). Components of dopamine signaling were further evaluated using mRNA profiling, immunohistochemistry, and pharmacological treatments. MEASUREMENTS AND RESULTS: Flies exposed to acute sleep deprivation on their first day of life showed impairments in short-term memory and response inhibition that persisted for at least 6 days. These impairments in adult performance were reversed by dopamine agonists, suggesting that the deficits were a consequence of reduced dopamine signaling. However, sleep deprivation did not impact dopaminergic neurons as measured by their number or by the levels of dopamine, pale (tyrosine hydroxylase), dopadecarboxylase, and the Dopamine transporter. However, dopamine pathways were impacted as measured by increased transcript levels of the dopamine receptors D2R and dDA1. Importantly, blocking signaling through the dDA1 receptor in animals that were sleep deprived during their critical developmental window prevented subsequent adult learning impairments. CONCLUSIONS: These data indicate that sleep plays an important and phylogenetically conserved role in the developing brain.

Ultra-high-b-value diffusion-weighted MR imaging for the detection of prostate cancer: evaluation in 201 cases with histopathological correlation.

PURPOSE: To assess the diagnostic performance of diffusion-weighted magnetic resonance (MR) imaging (DWI) for prostate cancer detection, using different b-values. METHODS: A total of 201 patients who underwent MR imaging before total prostatectomy were evaluated. MR images were independently assessed by three radiologists. Three combinations of sequences were separately evaluated, as follows: group 1 [T2-weighted images (T2WI) alone], group 2 (T2WI and DWI with a b-value of 1,000 s/mm2), group 3 (T2WI and DWI with a b-value of 2,000 s/mm2). Whole-mount-section histopathological examination was the reference standard. Areas under the receiver operating characteristic curve (AUCs) and diagnostic performance parameters were determined. RESULTS: The sensitivity, specificity, and AUC for the detection of prostate cancer were as follows: 52.2%, 80.7%, and 0.694 in group 1; 61.2%, 82.6%, and 0.755 in group 2; 73.2%, 89.7%, and 0.842 in group 3. Group 3 achieved the highest diagnostic performance, followed by group 2 (P<0.05). In the transition zone, the specificity was lower (P<0.001) for group 2 (82.2%) than for group 1 (86.2%). CONCLUSION: The addition of diffusion-weighted images with a b-value of 2,000 s/mm2 to T2WI can improve the diagnostic performance of MR imaging in prostate cancer detection.

The perilipin homologue, lipid storage droplet 2, regulates sleep homeostasis and prevents learning impairments following sleep loss.

Extended periods of waking result in physiological impairments in humans, rats, and flies. Sleep homeostasis, the increase in sleep observed following sleep loss, is believed to counter the negative effects of prolonged waking by restoring vital biological processes that are degraded during sleep deprivation. Sleep homeostasis, as with other behaviors, is influenced by both genes and environment. We report here that during periods of starvation, flies remain spontaneously awake but, in contrast to sleep deprivation, do not accrue any of the negative consequences of prolonged waking. Specifically, the homeostatic response and learning impairments that are a characteristic of sleep loss are not observed following prolonged waking induced by starvation. Recently, two genes, brummer (bmm) and Lipid storage droplet 2 (Lsd2), have been shown to modulate the response to starvation. bmm mutants have excess fat and are resistant to starvation, whereas Lsd2 mutants are lean and sensitive to starvation. Thus, we hypothesized that bmm and Lsd2 may play a role in sleep regulation. Indeed, bmm mutant flies display a large homeostatic response following sleep deprivation. In contrast, Lsd2 mutant flies, which phenocopy aspects of starvation as measured by low triglyceride stores, do not exhibit a homeostatic response following sleep loss. Importantly, Lsd2 mutant flies are not learning impaired after sleep deprivation. These results provide the first genetic evidence, to our knowledge, that lipid metabolism plays an important role in regulating the homeostatic response and can protect against neuronal impairments induced by prolonged waking.

The potential dermal irritating effect of residual (meth)acrylic monomers in pressure sensitive adhesive tapes.

It is generally thought that residual unpolymerized (meth)acrylic monomers commonly found in pressure sensitive adhesive tapes for medical use may cause dermal irritation, but a systematic study has never been carried out. Therefore, we assessed the potential dermal irritating effect of residual (meth)acrylic monomers. We studied seven acrylic monomers, acrylic acid (AA), methyl acrylate (MA), ethyl acrylate (EA), n-butyl acrylate (n-BA), n-hexyl acrylate (n-HA), 2-ethylhexyl acrylate (2-EHA) and 2-hydroxyethyl acrylate (HEA), as well as three methacrylic monomers, methacrylic acid (MAA), methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (2-HEMA). We first examined their cytotoxic effect on a cultured dermis model using the MTT method to determine their EC(50) and then performed a primary irritation test in rabbits using the monomers at three different concentrations (i.e., EC(50) , one-tenth EC(50) and 10 times EC(50)). Marked variations were found in cytotoxic and dermal irritating activities among the (meth)acrylic monomers tested. HEA exhibited the most potent dermal irritation having the lowest erythema dose (the concentration which gives a primary dermal irritation index of 1.00) of 460 ppm. But the other monomers exhibited less potent dermal irritation (lowest erythema doses > or =1000 ppm). For the monomers, significant correlation was found between cytotoxic activity and in vivo dermal irritating activity. Our results show that residual unpolymerized (meth)acrylic monomers in adhesive tapes are unlikely to induce skin irritation except for HEA. This study also suggests that cultured skin models are extremely useful as a screening method for chemical substances that could potentially cause dermal irritating activity.

Persistent short-term memory defects following sleep deprivation in a drosophila model of Parkinson disease.

STUDY OBJECTIVES: Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain. Thus we investigated the long-term consequences of sleep deprivation on shortterm memory using a Drosophila model of Parkinson disease. PARTICIPANTS: Transgenic strains of Drosophila melanogaster. DESIGN: Using the GAL4-UAS system, human alpha-synuclein was expressed throughout the nervous system of adult flies. Alpha-synuclein expressing flies (alpha S flies) and the corresponding genetic background controls were sleep deprived for 12 h at age 16 days and allowed to recover undisturbed for at least 3 days. Short-term memory was evaluated using aversive phototaxis suppression. Dopaminergic systems were assessed using mRNA profiling and immunohistochemistry. MEASURMENTS AND RESULTS: When sleep deprived at an intermediate stage of the pathology, alpha S flies showed persistent short-term memory deficits that lasted > or = 3 days. Cognitive deficits were not observed in younger alpha S flies nor in genetic background controls. Long-term impairments were not associated with accelerated loss of dopaminergic neurons. However mRNA expression of the dopamine receptors dDA1 and DAMB were significantly increased in sleep deprived alpha S flies. Blocking D1-like receptors during sleep deprivation prevented persistent shortterm memory deficits. Importantly, feeding flies the polyphenolic compound curcumin blocked long-term learning deficits. CONCLUSIONS: These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics.

Identifying sleep regulatory genes using a Drosophila model of insomnia.

Although it is widely accepted that sleep must serve an essential biological function, little is known about molecules that underlie sleep regulation. Given that insomnia is a common sleep disorder that disrupts the ability to initiate and maintain restorative sleep, a better understanding of its molecular underpinning may provide crucial insights into sleep regulatory processes. Thus, we created a line of flies using laboratory selection that share traits with human insomnia. After 60 generations, insomnia-like (ins-l) flies sleep 60 min a day, exhibit difficulty initiating sleep, difficulty maintaining sleep, and show evidence of daytime cognitive impairment. ins-l flies are also hyperactive and hyperresponsive to environmental perturbations. In addition, they have difficulty maintaining their balance, have elevated levels of dopamine, are short-lived, and show increased levels of triglycerides, cholesterol, and free fatty acids. Although their core molecular clock remains intact, ins-l flies lose their ability to sleep when placed into constant darkness. Whole-genome profiling identified genes that are modified in ins-l flies. Among those differentially expressed transcripts, genes involved in metabolism, neuronal activity, and sensory perception constituted over-represented categories. We demonstrate that two of these genes are upregulated in human subjects after acute sleep deprivation. Together, these data indicate that the ins-l flies are a useful tool that can be used to identify molecules important for sleep regulation and may provide insights into both the causes and long-term consequences of insomnia.

Cladosporium species-related hypersensitivity pneumonitis in household environments.

Home-related chronic hypersensitivity pneumonitis (HP) is sometimes difficult to discriminate because patients do not have an obvious history of antigen exposure. We report two HP cases which developed in an office area and in a home: a 47-year-old woman with acute-onset HP and a 72-year-old woman with chronic HP followed up as idiopathic pulmonary fibrosis following isolation of Cladosporium cladosporioides and Cladosporium herbarum, respectively. Lymphocyte stimulating activity and antibody titer to these fungi were increased in these patients. Since Cladosporium spp. and several other fungi are present ubiquitously in our living environment, it is difficult to eliminate the antigen from the patients' environment to control the disease. Cladosporium spp. can be key antigens in inducing chronic HP in the home environment.