Overcoming Current and Preventing Future Nosocomial Outbreaks during the COVID-19 Pandemic: Lessons Learned at Three Hospitals in Japan.

Hospitals are increasingly challenged by nosocomial infection (NI) outbreaks during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although standardized guidelines and manuals regarding infection prevention and control (IPC) measures are available worldwide, case-studies conducted at specified hospitals that are required to cope with real settings are limited. In this study, we analyzed three hospitals in Japan where large-scale NI outbreaks occurred for hints on how to prevent NI outbreaks. We reviewed openly available information from each hospital and analyzed it applying a three domain framework: operation management; identification of infection status; and infection control measures. We learned that despite having authorized infection control teams and using existing standardized IPC measures, SARS-CoV-2 may still enter hospitals. Early detection of suspected cases and confirmation by PCR test, carefully dealing with staff-to-staff transmission were the most essential factors to prevent NI outbreaks. It was also suggested that ordinary training on IPC for staff does not always provide enough practical knowledge and skills; in such cases external technical and operational supports are crucial. It is expected that our results will provide insights into preventing NI outbreaks of COVID-19, and contribute to mitigate the damage to health care delivery systems in various countries.

Exchange coupling in TbCu and DyCu single-molecule magnets and related lanthanide and vanadium analogs.

Heterometallic coordination compounds [Cu(II)(L)(C(3)H(6)O)Ln(III)(NO(3))(3)] and [V(IV)O(L)(C(3)H(6)O)Ln(III)(NO(3))(3)] (abbreviated as LnCu and LnV, respectively; H(2)L = N,N'-bis(3-methoxysalicylidene)-1,3-diamino-2,2-dimethylpropane; Ln = Gd, Tb, Dy, Ho, and Er) were synthesized, and the X-ray crystallographic analysis shows that their structures are isomorphous for each series. The single-molecule magnet behavior was observed for TbCu and DyCu, and the activation energies of magnetization reversal were 42.3(4) and 11.5(10) K, respectively. The magnetic exchange couplings in LnCu and LnV were precisely evaluated by means of combined high-frequency EPR and pulsed-field magnetization studies, to give J(Tb-Cu)/k(B)≥ 3.3 K, J(Dy-Cu)/k(B) = 1.63(1) K, J(Ho-Cu)/k(B) = 1.09(2) K, and J(Er-Cu)/k(B) = 0.24(1) K. A monotonic decrease of ferromagnetic J(Ln-Cu) was found in the order of the atomic number, (64)Gd to (68)Er. The corresponding exchange parameters in LnV are smaller than those of the Cu derivatives, and J(Gd-V) was antiferromagnetic (-3.0 K determined from the magnetization jump). A possible mechanism for the exchange coupling and chemical trend is discussed.

Chemical trend of Ln-M exchange couplings in heterometallic complexes with Ln = Gd, Tb, Dy, Ho, Er and M = Cu, V.

The 4f-3d exchange couplings were definitively and precisely determined in the dinuclear complexes (Ln-M) involving double µ-oxo-bridges, by means of combined high-frequency electron paramagnetic resonance and pulsed-field magnetization techniques, revealing a monotonic decrease of ferromagnetic J(Ln-Cu) in the order of the atomic number, (64)Gd to (68)Er.

[Cepharanthin effect on radiation-induced xerostomia and taste disorder in patients with head and neck cancer].

In evaluating the effect of cepharanthin on xerostomia and taste disorder in 40 patients undergoing radiotherapy for head and neck cancer, we administered cepharanthin intravenously during chemoradiotherapy to 22 patients, with 18 others as a control group. Cepharanthin did not significantly affect salivary secretion during and after chemoradiotherapy, although taste disorder and oral discomfort were alleviated. Cepharanthin may thus be effective in maintaining the quality of life of patients with head and neck cancer.

Distinct structural requirements for interleukin-4 (IL-4) and IL-13 binding to the shared IL-13 receptor facilitate cellular tuning of cytokine responsiveness.

Both interleukin-4 (IL-4) and IL-13 can bind to the shared receptor composed of the IL-4 receptor alpha chain and the IL-13 receptor alpha1 chain (IL-13Ralpha1); however, the mechanisms by which these ligands bind to the receptor chains are different, enabling the principal functions of these ligands to be different. We have previously shown that the N-terminal Ig-like domain in IL-13Ralpha1, called the D1 domain, is the specific and critical binding unit for IL-13. However, it has still remained obscure which amino acid has specific binding capacity to IL-13 and why the D1 domain acts as the binding site for IL-13, but not IL-4. To address these questions, in this study we performed mutational analyses for the D1 domain, combining the structural data to identify the amino acids critical for binding to IL-13. Mutations of Lys-76, Lys-77, or Ile-78 in c' strand in which the crystal structure showed interaction with IL-13, and those of Trp-65 and Ala-79 adjacent to the interacting site, resulted in significant impairment of IL-13 binding, demonstrating that these amino acids generate the binding site. Furthermore, mutations of Val-35, Leu-38, or Val-42 at the N-terminal beta-strand also resulted in loss of IL-13 binding, probably from decreased structural stability. None of the mutations employed here affected IL-4 binding. These results demonstrate that the D1 domain of IL-13Ralpha1 acts as an affinity converter, through direct cytokine interactions, that allows the shared receptor to respond differentially to IL-4 and IL-13.

Minimum spanning tree-based random-valued impulse noise detection for a switching median filter.

A switching median filter is effective for impulse noise elimination while preserving edges and details of an image. In the switching median filter an impulse noise detector is employed before filtering, and the detection result is used to control whether a pixel should be filtered or not. However, the conventional impulse detector tends to misjudge noise-free pixels constructing line structures to be the noises. We propose a new random-valued impulse noise detector based on the minimum spanning tree, and it is applied to the switching median filtering to eliminate the impulse noise effectively even for the image including line structures. Through the experiments, the effectiveness of the proposed random-valued impulse noise detector is illustrated.

Deaths from rotavirus disease in Bangladeshi children: estimates from hospital-based surveillance.

BACKGROUND: To assess the potential health benefits of introducing new rotavirus (RV) vaccines, we estimated mortality from RV gastroenteritis in Bangladeshi children <5 years of age. METHODS: We examined data from ongoing diarrhea surveillance in a systematic 2% sample (4% until 1995) of patients visiting the International Centre for Diarrheal Disease Research, Bangladesh, Dhaka Hospital during 1993-2004 and all patients visiting the rural Matlab Hospital during 2000-2004. To estimate deaths from RV, we multiplied the proportion of diarrhea visits attributable to RV with 2004 estimates of diarrhea deaths in Bangladeshi children. RESULTS: At Dhaka Hospital, RV was detected in 33% of 18,300 children with diarrhea. The proportion of diarrhea attributable to RV nearly doubled during 2002-2004 compared with 1993-1995 (42% versus 22%, P < 0.001). At Matlab Hospital, RV was detected in 35% of 4597 children with diarrhea. At both sites, most RV cases were among children age 3-24 months and the number of cases peaked during the cool and dry months from December through February. Of the 325,600 deaths among children <5 years that occur each year, we estimated 5600 to 9400 (2-3%) were attributable to RV. Thus, between 1 in 390 and 1 in 660 children born in Bangladesh each year die of RV infection by age 5. CONCLUSIONS: These data clearly demonstrate the tremendous health burden of RV gastroenteritis. The increasing proportion of severe diarrhea cases underscores the need for specific interventions against RV, such as vaccines, to further reduce diarrhea mortality and morbidity.

Involvement of IL-32 in activation-induced cell death in T cells.

NK cell transcript 4 (NK4), now denoted as IL-32, was originally identified as a transcript whose expression was increased in activated NK cells. It has been very recently demonstrated that NK4 is secreted from several cells upon the stimulation of some inflammatory cytokines such as IL-18, IL-1beta, IFN-gamma and IL-12. Furthermore, NK4 induces production of tumor necrosis factor, macrophage inflammatory protein (MIP)-2 and IL-8 in monocytic cell lines, indicating that this factor would be involved in the inflammatory responses. Based on these findings, NK4 was renamed IL-32. However, the biological activities of IL-32 on other cell types remained undetermined. Furthermore, it was still argued whether IL-32 acts on cells from outside or inside the cells. In this article, we first report that expression of IL-32 was up-regulated in activated T cells and NK cells, and that IL-32beta was the predominantly expressed isoform in activated T cells. IL-32 was specifically expressed in T cells undergoing apoptosis and enforced expression of IL-32-induced apoptosis, whereas its down-regulation rescued the cells from apoptosis in HeLa cells. IL-32 existing in the supernatant would be derived from the cytoplasm of apoptotic cells. These results strongly indicated that IL-32 would be involved in activation-induced cell death in T cells, probably via its intracellular actions. Our present findings expand our understanding of the biological function of IL-32 and argue that IL-32 may act on cells, not only from the outside but also from the inside.

Characterization of the interaction between interleukin-13 and interleukin-13 receptors.

Interleukin-13 (IL-13) possesses two types of receptor: the heterodimer, composed of the IL-13Ralpha1 chain (IL-13Ralpha1) and the IL-4Ralpha chain (IL-4Ralpha), transducing the IL-13 signals; and the IL-13Ralpha2 chain (IL-13Ralpha2), acting as a nonsignaling "decoy" receptor. Extracellular portions of both IL-13Ralpha1 and IL-13Ralpha2 are composed of three fibronectin type III domains, D1, D2, and D3, of which the last two comprise the cytokine receptor homology modules (CRHs), a common structure of the class I cytokine receptor superfamily. Thus far, there has been no information about the critical amino acids of the CRHs or the role of the D1 domains of IL-13Ralpha1 and IL-13Ralpha2 in binding to IL-13. In this study, we first built the homology modeling of the IL-13.hIL-13 receptor complexes and then predicted the amino acids involved in binding to IL-13. By incorporating mutations into these amino acids, we identified Tyr-207, Asp-271, Tyr-315, and Asp-318 in the CRH of human IL-13Ralpha2, and Leu-319 and Tyr-321 in the CRH of human IL-13Ralpha1, as critical residues for binding to IL-13. Tyr-315 in IL-13Ralpha2 and Leu-319 in IL-13Ralpha1 are positionally conserved hydrophobic amino acid residues. Furthermore, by using D1 domain-deleted mutants, we found that the D1 domain is needed for the expression of IL-13Ralpha2, but not IL-13Ralpha1, and that the D1 domain of IL-13Ralpha1 is important for binding to IL-13, but not to IL-4. These results provide the basis for a precise understanding of the interaction between IL-13 and its receptors.

Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells.

It is widely known that IL-4 and IL-13 act on various kinds of cells, including B cells, resulting in enhancement of proliferation, class switching to IgE and expression of several surface proteins. These functions are important for the recognition of the various antigens in B cells and are known to be involved in the pathogenesis of allergic diseases. However, it has not been known whether IL-4/IL-13 is involved in the metabolism of various kinds of xenobiotics including 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), and it remains undetermined whether TCDD, an environmental pollutant, influences IgE production in B cells, exaggerating allergic reactions. We identified IL-4- or IL-13-inducible genes in a human Burkitt lymphoma cell line, DND-39, using microarray technology, in which the AHR gene was included. The AHR gene product, the aryl hydrocarbon receptor (AhR), was induced by IL-4 in both mouse and human B cells in a STAT6-dependent manner. IL-4 alone had the ability to translocate the induced AhR to the nuclei. TCDD, a ligand for AhR, rapidly degraded the induced AhR by the proteasomal pathway, although IL-4-activated AhR sustained its expression. AhR activated by IL-4 caused expression of a xenobiotic-metabolizing gene, CYP1A1, and TCDD synergistically acted on the induction of this gene by IL-4. However, the induction of AhR had no effect on IgE synthesis or CD23 expression. These results indicate that the metabolism of xenobiotics would be a novel biological function of IL-4 and IL-13 in B cells, whereas TCDD is not involved in IgE synthesis in B cells.