Surge of Typhoid Intestinal Perforations as Possible Result of COVID-19-Associated Delays in Seeking Care, Madagascar.

During the coronavirus disease pandemic, we observed a 6.4-fold increase in typhoid intestinal perforation incidence in Antananarivo, Madagascar. Thirteen perforations occurred within 6 months (February 2020-July 2020), compared with 13 perforations during the previous 41 months (August 2016-January 2020). The increase may be attributable to delayed healthcare seeking during the pandemic

Effect of high cobalt concentration on hopping motion in cobalt manganese spinel oxide (CoxMn3–xO4,x≥ 2.3)

Hopping motions in cobalt manganese spinel oxides with high cobalt concentration (CoxMn3−xO4, 2.3 ≤ x ≤ 2.7) are investigated in order to clarify the origin of unusual electrical behaviors as negative temperature coefficient (NTC) thermistors. Based on the resistance versus temperature (R−T) characteristics, hopping conduction mechanisms in MCO compounds (x = 2.3 and 2.5) are attributed to variable range hopping (VRH) motion with a parabolic distribution of the density of states (DOS) near the Fermi level. However, when Co content increases up to 2.7, transition in the hopping motion occurs from VRH to the nearest neighboring hopping (NNH) motion, which can be responsible for a huge increase of the resistance accompanied by decrease of the factor of thermal sensitivity (B value) in MCO compounds (x = 2.7). Also, hopping distance and activation energies for MCO (x = 2.3 and 2.5) compounds following VRH conduction are calculated as a function of temperature, indicating that higher B value observed in MCO (x = 2.5) compound is due to the larger hopping distance compared to that of MCO (x = 2.3) compound

Transcriptional Profiling Shows Altered Expression of Wnt Pathway– and Lipid Metabolism–Related Genes as Well as Melanogenesis-Related Genes in Melasma

Melasma is a commonly acquired hyperpigmentary disorder of the face, but its pathogenesis is poorly understood and its treatment remains challenging. We conducted a comparative histological study on lesional and perilesional normal skin to clarify the histological nature of melasma. Significantly, higher amounts of melanin and of melanogenesis-associated proteins were observed in the epidermis of lesional skin, and the mRNA level of tyrosinase-related protein 1 was higher in lesional skin, indicating regulation at the mRNA level. However, melanocyte numbers were comparable between lesional and perilesional skin. A transcriptomic study was undertaken to identify genes involved in the pathology of melasma. A total of 279 genes were found to be differentially expressed in lesional and perilesional skin. As was expected, the mRNA levels of a number of known melanogenesis-associated genes, such as tyrosinase, were found to be elevated in lesional skin. Bioinformatics analysis revealed that the most lipid metabolism-associated genes were downregulated in lesional skin, and this finding was supported by an impaired barrier function in melasma. Interestingly, a subset of Wnt signaling modulators, including Wnt inhibitory factor 1, secreted frizzled-related protein 2, and Wnt5a, were also found to be upregulated in lesional skin. Immunohistochemistry confirmed the higher expression of these factors in melasma lesions

High density of ice krill (Euphausia crystallorophias) in the Amundsen sea coastal polynya, Antarctica

High densities of ice krill Euphausia crystallorophias were observed along six acoustic transects within the Amundsen Sea Coastal Polynya, Antarctica. Two-frequency acoustic backscatter data was examined in the austral summers of January 2011 and February 2012. A dB identification window (Sv120−38) identified ice krill dominating the acoustic backscatter. The density of ice krill, calculated with the stochastic distorted-wave born approximation model, ranged between 4.5 and 30 g wet mass m−2 for each transect (a mean of 16 g wet mass m−2 for all transects), these high values are an order of magnitude higher than recorded previously in the Ross Sea Polynya. High densities were detected along the ice shelf and near the boundary between pack ice and coastal polynya, and we postulate that these could be important habitats for ice krill. The high densities observed along the transects make ice krill a potentially important, but poorly known contributor to these high-latitude shelf food webs

Clinical Characteristics of Radiation Oncology in Korea during Past 10 Years

To understand trends in the clinical characteristics of radiation oncology over the last 10 yr in Korea, annual survey questionnaires were sent to all of Korean radiation oncology facilities since 1990. Questionnaires addressed basic radiation therapy facilities and the clinical information. Responses were obtained from all facilities, and data collected from 1997 to 2006 was analyzed. The numbers of new patients that have undergone radiation therapy and the numbers of hospitals with a department of radiation oncology have steadily increased over the past 10 yr, and totaled 37,215 patients and 60 hospitals, respectively, in 2006. However, the proportion of patients irradiated among total cancer patients has remained below 30% over the last 10 yr. The numbers of prostate cancer, breast cancer, and hepatoma have increased by more than 3 fold over the past 10 yr. Moreover, the percentage of irradiated patients treated by brachytherapy was 10.3% in 1997, but this gradually fell to only 4.2% in 2006. The information collected described the role played by radiation oncology in Korea. Continuous surveys are required to enable trends to be detected

Kaposi's sarcoma-associated herpesvirus ORF57 protein: exploiting all stages of viral mRNA processing

Nuclear mRNA export is a highly complex and regulated process in cells. Cellular transcripts must undergo successful maturation processes, including splicing, 5'-, and 3'-end processing, which are essential for assembly of an export competent ribonucleoprotein particle. Many viruses replicate in the nucleus of the host cell and require cellular mRNA export factors to efficiently export viral transcripts. However, some viral mRNAs undergo aberrant mRNA processing, thus prompting the viruses to express their own specific mRNA export proteins to facilitate efficient export of viral transcripts and allowing translation in the cytoplasm. This review will focus on the Kaposi’s sarcoma-associated herpesvirus ORF57 protein, a multifunctional protein involved in all stages of viral mRNA processing and that is essential for virus replication. Using the example of ORF57, we will describe cellular bulk mRNA export pathways and highlight their distinct features, before exploring how the virus has evolved to exploit these mechanisms

CD4+ T Cell Dependent B Cell Recovery and Function After Autologous Hematopoietic Stem Cell Transplantation

Introduction: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) represents a standard treatment regime for multiple myeloma (MM) patients. Common and potentially fatal side effects after auto-HSCT are infections due to a severely compromised immune system with hampered humoral and cellular immunity. This study delineates in depth the quantitative and functional B cell defects and investigates underlying extrinsic or intrinsic drivers. Methods: Peripheral blood of MM patients undergoing high-dose chemotherapy and auto-HSCT (before high-dose chemotherapy and in early reconstitution after HSCT) was studied. Absolute numbers and distribution of B cell subsets were analyzed ex vivo using flow cytometry. Additionally, B cell function was assessed with T cell dependent (TD) and T cell independent (TI) stimulation assays, analyzing proliferation and differentiation of B cells by flow cytometry and numbers of immunoglobulin secreting cells in ELISpots. Results: Quantitative B cell defects including a shift in the B cell subset distribution occurred after auto-HSCT. Functionally, these patients showed an impaired TD as well as TI B cell immune response. Individual functional responses correlated with quantitative alterations of CD19+, CD4+, memory B cells and marginal zone-like B cells. The TD B cell function could be partially restored upon stimulation with CD40L/IL-21, successfully inducing B cell proliferation and differentiation into plasmablasts and immunoglobulin secreting cells. Conclusion: Quantitative and functional B cell defects contribute to the compromised immune defense in MM patients undergoing auto-HSCT. Functional recovery upon TD stimulation and correlation with CD4+ T cell numbers, indicate these as extrinsic drivers of the functional B cell defect. Observed correlations of CD4+, CD19+, memory B and MZ-like B cell numbers with the B cell function suggest that these markers should be tested as potential biomarkers in prospective studies

Observation of SQUID-like behavior in fiber laser with intra-cavity epsilon-near-zero effect

Establishing relations between fundamental effects in far-flung areas of physics is a subject of great interest in the current research. We here report realization of a novel photonic system akin to the radio-frequency superconducting quantum interference device (RF-SQUID), in a fiber laser cavity with epsilon-near-zero (ENZ) nanolayers as intra-cavity components. Emulating the RF-SQUID scheme, the photonic counterpart of the supercurrent, represented by the optical wave, circulates in the cavity, passing through effective optical potential barriers. Different ENZ wavelengths translate into distinct spectral outputs through the variation of cavity resonances, emulating the situation with a frequency-varying tank circuit in the RF-SQUID. Due to the presence of the ENZ element, the optical potential barrier is far lower for selected frequency components, granting them advantage in the gain-resource competition. The findings reported in this work provide a deeper insight into the ultrafast ENZ photonics, revealing a new path towards the design of nanophotonic on-chip devices with various operational functions, and offer a new approach to study superconducting and quantum-mechanical systems.Comment: to be published in Laser & Photonics Review

HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients

The inability of patients with CVID to mount specific antibody responses to pathogens has raised concerns on the risk and severity of SARS-CoV-2 infection, but there might be a role for protective T cells in these patients. SARS-CoV-2 reactive T cells have been reported for SARS-CoV-2 unexposed healthy individuals. Until now, there is no data on T cell immunity to SARS-CoV-2 infection in CVID. This study aimed to evaluate reactive T cells to human endemic corona viruses (HCoV) and to study pre-existing SARS-CoV-2 reactive T cells in unexposed CVID patients. We evaluated SARS-CoV-2- and HCoV-229E and -OC43 reactive T cells in response to seven peptide pools, including spike and nucleocapsid (NCAP) proteins, in 11 unexposed CVID, 12 unexposed and 11 post COVID-19 healthy controls (HC). We further characterized reactive T cells by IFNγ, TNFα and IL-2 profiles. SARS-CoV-2 spike-reactive CD4+ T cells were detected in 7 of 11 unexposed CVID patients, albeit with fewer multifunctional (IFNγ/TNFα/IL-2) cells than unexposed HC. CVID patients had no SARS-CoV-2 NCAP reactive CD4+ T cells and less reactive CD8+ cells compared to unexposed HC. We observed a correlation between T cell reactivity against spike of SARS-CoV-2 and HCoVs in unexposed, but not post COVID-19 HC, suggesting cross-reactivity. T cell responses in post COVID-19 HC could be distinguished from unexposed HC by higher frequencies of triple-positive NCAP reactive CD4+ T cells. Taken together, SARS-CoV-2 reactive T cells are detectable in unexposed CVID patients albeit with lower recognition frequencies and polyfunctional potential. Frequencies of triple-functional reactive CD4+ cells might provide a marker to distinguish HCoV cross-reactive from SARS-CoV-2 specific T cell responses. Our data provides evidence, that anti-viral T cell immunity is not relevantly impaired in most CVID patients

AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha 2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. in contrast, AgRPa2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha 2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus