Clinical impact of physician staffing transition in intensive care units: a retrospective observational study.

BACKGROUND: Intensivists play an essential role in improving the outcomes of critically ill patients in intensive care units (ICUs). The transition of ICU physician staffing from low-intensity ICUs (elective intensivist or no intensivist consultation) to high-intensity ICUs (mandatory intensivist consultation or a closed ICU) improves clinical outcomes. However, whether a transition from high-intensity to low-intensity ICU staffing affects ICU outcomes and quality of care remains unknown. METHODS: A retrospective observational study was conducted to examine the impact of high- versus low-intensity staffing models on all-cause mortality in a suburban secondary community hospital with 400 general beds and 8 ICU beds. The ICU was switched from a high-intensity staffing model (high-former period) to low-intensity staffing in July 2019 (low-mid period) and then back to high-intensity staffing in March 2020 (high-latter period). Patients admitted from the emergency department, general ward, or operating room after emergency surgery were enrolled in these three periods and compared, balancing the predicted mortality and covariates of the patients. The primary outcome was all-cause mortality analyzed using hazard ratios (HRs) from Cox proportional hazards regression. An interrupted time-series analysis (ITSA) was also conducted to evaluate the effects of events (level change) and time. RESULTS: There were 962 eligible admissions, of which 251, 213, and 498 occurred in the high-former, low-mid, and high-latter periods, respectively. In the matched group (n = 600), the all-cause mortality rate comparing the high-former period with the low-mid period showed an HR of 0.88 [95% confidence interval (CI), 0.56, 1.39; p = 0.58] and that comparing the high-latter period with the low-mid period showed an HR of 0.84 [95% CI, 0.54, 1.30; p = 0.43]. The result for comparison between the three periods was p = 0.80. ITSA showed level changes of 4.05% [95% CI, -13.1, 21.2; p = 0.63] when ICU staffing changed from the high-former to the low-mid period and 1.35% [95% CI, -13.8, 16.5; p = 0.86] when ICU staffing changed from the low-mid to the high-latter period. CONCLUSION: There was no statistically significant difference in all-cause mortality among the three ICU staffing periods. This study suggests that low-intensity ICU staffing might not worsen clinical outcomes in the ICU in a medium-sized community hospital. Multiple factors, including the presence of an intensivist, other medical staff, and practical guidelines, influence the prognosis of critically ill patients.

Gut bacterial aromatic amine production: aromatic amino acid decarboxylase and its effects on peripheral serotonin production.

Colonic luminal aromatic amines have been historically considered to be derived from dietary source, especially fermented foods; however, recent studies indicate that the gut microbiota serves as an alternative source of these amines. Herein, we show that five prominent genera of Firmicutes (Blautia, Clostridium, Enterococcus, Ruminococcus, and Tyzzerella) have the ability to abundantly produce aromatic amines through the action of aromatic amino acid decarboxylase (AADC). In vitro cultivation of human fecal samples revealed that a significant positive correlation between aadc copy number of Ruminococcus gnavus and phenylethylamine (PEA) production. Furthermore, using genetically engineered Enterococcus faecalis-colonized BALB/cCrSlc mouse model, we showed that the gut bacterial aadc stimulates the production of colonic serotonin, which is reportedly involved in osteoporosis and irritable bowel syndrome. Finally, we showed that human AADC inhibitors carbidopa and benserazide inhibit PEA production in En. faecalis.

Pulmonary vein thrombosis and cerebral infarction after video-assisted thoracic surgery of the left upper lobe: a case series.

BACKGROUND: Pulmonary vein thrombosis (PVT) and cerebral infarction are rare but critical complications after video-assisted thoracic surgery (VATS). CASE PRESENTATION: We experienced two cases of massive middle cerebral artery infarction after VATS for the left upper lobe. Although the precise source of their embolus was never identified, both cases were clinically suspected PVT. Unfortunately, case 2 died because of progressive cerebral herniation. We decided to perform contrast-enhanced computed tomography routinely after VATS for the left upper lobectomy (VATS-LUL) after these cases. Case 3, a 79-year-old female patient, underwent VATS-LUL for lung cancer. She developed PVT in the stump of the left upper pulmonary vein on postoperative day 4. Anti-coagulation therapy was begun immediately and continued for 3 months. She was free of complications 7 months after the operation. CONCLUSION: PVT and cerebral infarction may occur after VATS-LUL. Appropriate postoperative management is required to recognize PVT and to prevent life-threatening stroke.

Distinct Skin Microbiome and Skin Physiological Functions Between Bedridden Older Patients and Healthy People: A Single-Center Study in Japan.

With the increase in the older populations, the number of bedridden older patients is becoming a matter of concern. Skin microbiome and skin physiological functions are known to change according to lifestyle and community; however, such changes in case of movement- and cleaning-restricted bedridden older patients have not yet been revealed. To address this issue, we analyzed skin microbiome and skin physiological functions, including pH, hydration, sebum level, and transepidermal water loss (TEWL), of bedridden older patients, compared with those of ambulatory older and young individuals. For this analysis, we enrolled 19 healthy young and 18 ambulatory older individuals from the community and 31 bedridden older patients from a single, long-term care hospital in Japan. The area of interest was set to the sacral (lower back) skin, where pressure injuries (PIs) and subsequent infection frequently occurs in bedridden older patients. We observed a higher number of gut-related bacteria, fewer commensals, higher skin pH, and lower TEWL on the sacral skin of bedridden older patients than on that of young or ambulatory older individuals. In addition, we observed that 4 of the 31 bedridden older patients developed PIs during the research period; a higher abundance of pathogenic skin bacteria were also observed inside the PI wounds. These findings imply distinct skin microbiome and skin physiological functions in bedridden older patients in comparison with healthy individuals and may suggest the need for more stringent cleaning of the skin of bedridden older patients in light of the closeness of skin and wound microbiome.

Measuring the Antimicrobial Activity of Lauric Acid against Various Bacteria in Human Gut Microbiota Using a New Method.

Lauric acid (LA) has a broad spectrum of anti-microbiological activities against enveloped viruses and various bacteria, and might be useful to protect against microbial infection and control the balance and distribution of bacteria in human gut microbiota. It is not necessarily more difficult to measure antimicrobial activity the traditional way, but it is, however, more laborious. In the present study, we developed a new method to measure the antimicrobial activity of LA in multiple samples with a microplate reader. A "test complex" (TC) was produced consisting of 100 µL of agar medium with LA in the bottom layer and 300 µL of broth in the top layer in 96-well deep-well microplates. Afterward, analysis of the broth in the top layer showed that the antimicrobial activity was the same as that of the "control complex," (CC) which consisted of 100 µL of agar medium in the bottom layer and 300 µL of broth with LA in the top layer. Furthermore, evaluation of the antimicrobial effect of the TC when using a microplate reader was the same as that with the use of the colony counting method. The colony counting method has confirmed that the antimicrobial activity of LA when bacteria are inoculated into the broth was equivalent between CC and TC, and we validated this by correlating the number of bacteria with absorbance. In addition, the broth itself in TC was transparent enough that the turbidity of broth can be used as an index of the number of bacteria, which enabled the use of a microplate reader for multiple samples. For human gut microbes, LA was shown to have low antimicrobial activity against commensal lactic acid bacteria, but high antimicrobial activity against pathogenic Bacteroides and Clostridium, suggesting that LA might modulate intestinal health, as confirmed by the proposed method.

Corrigendum: A Comparison of Techniques for Collecting Skin Microbiome Samples: Swabbing Versus Tape-Stripping.

[This corrects the article DOI: 10.3389/fmicb.2018.02362.].

A Comparison of Techniques for Collecting Skin Microbiome Samples: Swabbing Versus Tape-Stripping.

The swabbing and tape-stripping methods have traditionally been used for collecting skin microbiome samples for skin bacterial analysis, although no reports have compared the outcome of these methods for collecting skin bacteria. Our purpose was to show the differences in microbial composition between samples collected using the swabbing and tape-stripping methods, by both the next generation sequencing and culture studies. The skin microbiome was collected by both methods, and the samples were processed for a sequence-based microbiome analysis and culture study. The next-generation sequencing results showed that skin bacteria collected using the tape-stripping method were comparable to those collected using the swabbing method. In the culture study, the tape-stripping method collected a greater number and wider variety of viable skin bacteria than the swabbing method. These results suggest that the tape-stripping method is comparable to the swabbing method for collecting viable skin bacteria, without losing fidelity to the composition of skin microbiome.

The Effect of Music on Exercise Intensity among Children with Autism Spectrum Disorder: A Pilot Study.

Children with autism spectrum disorder (ASD) are at risk for obesity, commonly have sleep disorders, and exhibit stereotypic behaviors that disrupt their learning. Vigorous levels of exercise have been shown to ameliorate these issues in children with ASD, but little research exists to provide techniques for motivating children with ASD to engage in exercise. The present study examined the effect of music on exercise intensity in a group of 13 elementary school students with ASD. Data were collected across six days during structured (e.g., verbal and physical prompts) and unstructured (e.g., minimal prompting) exercise periods. During these exercise periods, three music conditions were randomized: no music, slow-tempo music, and fast-tempo music. Exercise intensity, measured in Metabolic Equivalent of Tasks by triaxial accelerometers, was greatest during the structured exercise periods and during the slow music condition. Student characteristics moderated the impact of music condition on exercise intensity, such that students with high levels of adaptive behavior or lower levels of maladaptive behavior displayed greater exercise intensity during the fast music condition.

[Perioperative management for a case of carotid artery stenting].

A 70-year-old male patient with severe cardiac dysfunction underwent carotid artery stenting for severe left carotid artery stenosis under monitored anesthetic care. He was sedated with propofol and fentanyl, and was monitored with ECG, pulse-oximeter and direct blood pressure measurement. He breathed spontaneously without severe hypoxia during the procedure. Followed by insertion of transient ventricular pacing wire against expected severe bradycardia, a guidewire was introduced into left internal carotid artery lesion via the right femoral artery. Soon after dilating the stenotic portion with a ballon catheter, sudden hypotension and bradycardia were recognized, which were successfully managed with bolus injections of vasoconstrictors and atropine sulphate. Even after stenting, hypotension continued for two days in spite of continuous administration of dopamine. Postoperative examination showed that the blood flow of the left carotid artery was doubled. Two weeks after the operation, he was discharged uneventfully.

Molecular cytogenetic characterization of telomere-specific repetitive DNA sequences in Rana rugosa.

We performed a molecular cloning of the glutamic oxaloacetic transaminase (GOT1) gene from R. rugosa, and determined its chromosomal location. This gene was reportedly localized near the sex-determining region of the ZW sex chromosomes in the frog Buergeria buergeri; however, the GOT1 gene was mapped to the distal end of chromosome 9 in R. rugosa using a GOT1 cDNA FISH probe. This was also the case when a 46.3 kb genomic clone containing exon 8 and 9 and the 3'-neighboring region of the GOT1 gene, designated clone B, was used as probe. However, weak signals were also detected at the telomeric ends of other autosomes and the Z sex chromosome, and near the centromeric region of the W sex chromosome. To intensify the signals, we used eight internal fragments in clone B and applied them to chromosome mapping. Consequently, only two fragments containing repeated sequence blocks produced hybridization signals; those signals were observed on autosomes and ZW sex chromosomes. The 3'-neighboring region contained two types of repeated sequence elements: a 41 bp element, designated 41-REL, localized to telomeric ends of autosomes and a 31 bp element, designated 31-REL, localized to telomeric ends of all autosomes and the ZW sex chromosomes, and also near the centromere on the W long arm. The results collectively suggest that the two repeated sequence elements were independently amplified around the chromosomal telomeres in R. rugosa, indicating that they will be useful cytogenetic markers for studying karyotypic evolution-especially the W chromosome differentiation-in this species.

A novel insertion mutation of K294RGG within BCR-ABL kinase domain confers imatinib resistance: sequential analysis of the clonal evolution in a patient with chronic myeloid leukemia in blast crisis.

BCR-ABL kinase domain mutations were sequentially analyzed in a patient with chronic myeloid leukemia (CML) who exhibited repeated B-lymphoid blast crisis (CML-BC) during treatment with imatinib and dasatinib. We first identified five mutant BCR-ABL clones: Y253H, G250E, F311L, F317L and K294RGG, which was generated by two-nucleotide mutations and six-nucleotide insertion, at the third BC during the imatinib treatment, and retrospectively found that three of them (Y253H, G250E, K294RGG) were already present at the second BC. The in vitro analysis using K294RGG mutant BCR-ABL-expressing 32D cells revealed that K294RGG mutation was imatinib resistant but dasatinib sensitive. Consistent with the in vitro data, the clone with K294RGG mutation was eliminated by the dasatinib treatment in this patient. During the imatinib treatment, several mutant clones emerged and expanded, while additional mutations on the same allele were not acquired. However, after the dasatinib treatment, wild-type BCR-ABL clone disappeared and T315I or F317L mutation was acquired in G250E and Y253H mutant clones on the same allele without the emergence of each sole mutant clone. Cytogenetic and immunoglobulin heavy chain gene rearrangement analysis revealed that all mutant clones that appeared in this patient might be derived from the same CML clone.

Selective KIT inhibitor KI-328 and HSP90 inhibitor show different potency against the type of KIT mutations recurrently identified in acute myeloid leukemia.

Activating mutations of KIT play an important role in the pathophysiology of several human malignancies, including acute myeloid leukemia. Activated KIT kinase is therefore a promising molecular target for the treatment of many malignancies harboring KIT activation. Here we examined the potency of a novel KIT inhibitor KI-328 against different types of mutant KIT kinases recurrently identified in AML. KI-328 shows selective potency against KIT kinase for the in vitro kinase assay, and inhibits the growth of wild-type (Wt)- and mutant-KIT-expressing cells, while it has little potency against D816V-KIT. Comparable analysis of several potent KIT inhibitors regarding growth inhibitory effects on a variety of mutant-KIT-expressing cells revealed that multi-kinase inhibitors have the same potency against D816V-KIT as other mutant KITs; however, the predominant potency against D816V-KIT was observed in heat shock protein 90 (HSP90) inhibitors. Furthermore, HSP90 inhibitors suppress the growth of D816V-KIT-expressing cells at the concentration at which the growth of other mutant-KIT-expressing cells is not affected. These results collectively indicated that potent KIT inhibitors have different potency against the type of mutant KIT kinases. Therefore, KIT inhibitors are required to validate potency against several types of mutant KIT kinases for the clinical development.

[A case of the complications following glycerin enema which suggested malignant hyperthermia].

We experienced a case of the complications following glycerin enema which suggested malignant hyperthermia. A 73-year-old man with knee osteoarthritis was scheduled for total knee arthroplasty under general and epidural anesthesia. The patient received glycerin enema before surgery. After epidural catheterization, anesthesia was induced with thiopental, fentanyl, vecuronium and sevoflurane. The trachea was intubated and the patient was ventilated with sevoflurane-air-oxygen. Then, cola-like urine was drained and he became febrile up to 37.9 degrees C. Although there were no other symptoms suggesting malignant hyperthermia, the surgery was cancelled. We suspected not only hemolysis by the color of the serum and the blood chemistry, but also rhabdomyolysis by increased levels of serum creatine phosphokinase and myoglobin as well as urine myoglobin. He recovered uneventfully. On the third day, perirectal abscess and anal fissure were diagnosed, which were considered to be the cause of the fever. It is well-known that glycerin enema could cause hemolysis, but rabdomyolysis as a complication of glycerin enema has rarely been reported. We speculate that injection of hypertonic glycerin into the perirectal tissue could have caused rhabdomyolysis as well as hemolysis, which led to cola-like urine. The complications following glycerin enema can be incorporated to a differential diagnosis of malignant hyperthermia.

KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation.

KW-2449, a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase, is under investigation to treat leukemia patients. In this study, we examined its possible modes of action for antileukemic effects on FLT3-activated, FLT3 wild-type, or imatinib-resistant leukemia cells. KW-2449 showed the potent growth inhibitory effects on leukemia cells with FLT3 mutations by inhibition of the FLT3 kinase, resulting in the down-regulation of phosphorylated-FLT3/STAT5, G(1) arrest, and apoptosis. Oral administration of KW-2449 showed dose-dependent and significant tumor growth inhibition in FLT3-mutated xenograft model with minimum bone marrow suppression. In FLT3 wild-type human leukemia, it induced the reduction of phosphorylated histone H3, G(2)/M arrest, and apoptosis. In imatinib-resistant leukemia, KW-2449 contributed to release of the resistance by the simultaneous down-regulation of BCR/ABL and Aurora kinases. Furthermore, the antiproliferative activity of KW-2449 was confirmed in primary samples from AML and imatinib-resistant patients. The inhibitory activity of KW-2449 is not affected by the presence of human plasma protein, such as alpha1-acid glycoprotein. These results indicate KW-2449 has potent growth inhibitory activity against various types of leukemia by several mechanisms of action. Our studies indicate KW-2449 has significant activity and warrants clinical study in leukemia patients with FLT3 mutations as well as imatinib-resistant mutations.

Tyk2 is essential for IFN-alpha-induced gene expression in mast cells.

Mast cells are recognized not only as the major effector cells of type I hypersensitivity reactions but also as an important player of innate immune response against bacterial infection. Type I IFNs are also involved in the response against bacterial infection. However, the role of type I IFNs and their associated Janus kinase Tyk2 in mast cell functions remains to be determined. In this study, we addressed this issue using Tyk2-deficient (Tyk2(-/-)) bone marrow-derived mast cells (BMMCs). When BMMCs from wild-type (WT) mice were stimulated with IFN-alpha, they expressed mRNA for IFN-gamma-inducible protein 10 (IP-10) and monocyte chemoattractant protein-5 (MCP-5). Interestingly, IFN-alpha-induced expression of IP-10 and MCP-5 was severely decreased in Tyk2(-/-) BMMCs. In addition, IFN-alpha-induced Stat1 phosphorylation was decreased in Tyk2(-/-) BMMCs. On the other hand, IFN-alpha-induced Stat1 phosphorylation and IP-10 and MCP-5 expression were normal in Tyk2(-/-) fibroblasts. These results indicate that IFN-alpha induces the expression of TNF-alpha and the chemokines IP-10 and MCP-5 in mast cells and thatTyk2 plays a nonredundant role in IFN-alpha signaling in mast cells.

Diastereoselective allylations of allyl-propargyl hybrid cations: synthesis of conjugated 1,5-dien-7-yne frameworks bearing C(4)-stereogenic centers.

[reaction: see text] Chiral C(4)-substituted (E)- or (Z)-1-alkynyl-1-trimethylsilyloxy-2-butene systems provide anti-(Z) or syn-(Z) conjugated dienyne, with a very high level of stereocontrol, on treatment with BF(3).OEt(2) in CH(2)Cl(2) at -50 degrees C in the presence of allyltrimethylsilane. The Cieplak conformation for (E)-substrates and neighboring-group participation for (Z)-substrates are considered to be responsible for the stereochemical consequences.

Lewis acid-catalyzed nucleophilic substitutions of propargylic and allylic silyl ethers with enol silyl ethers.

Nucleophilic reactions of various enol silyl ethers with carbocation species generated from propargyl silyl ethers by the action of a Lewis acid have been developed. The present method is highly useful for the introduction of allenic or enyne functionalities into the alpha-position of substituted ketones. [reaction--see text]

A case of solitary necrotic nodule of the liver with acute liver dysfunction: The imaging appearance correlated with pathological findings.

A 22-year-old woman was admitted to this institution because of severe liver dysfunction that looked like acute hepatitis. Abdominal ultrasonography revealed a liver mass 20 mm in diameter that resembled the bull's-eye sign. Enhanced CT revealed a low-density mass. The mass was hypointense in T1-weighted MRI images and slightly hyperintense in T2-weighted MRI images. Needle biopsy of the liver under ultrasound guidance led to a diagnosis of solitary necrotic nodule of the liver. The tumor consisted of coagulation necrosis surrounded by fibrotic tissue. These pathologic features were consistent with the Imaging findings.