Atypical lymphocytes in the peripheral blood of COVID-19 patients: A prognostic factor for the clinical course of COVID-19.

BACKGROUND: Clinical observations have shown that there is a relationship between coronavirus disease 2019 (COVID-19) and atypical lymphocytes in the peripheral blood; however, knowledge about the time course of the changes in atypical lymphocytes and the association with the clinical course of COVID-19 is limited. OBJECTIVE: Our purposes were to investigate the dynamics of atypical lymphocytes in COVID-19 patients and to estimate their clinical significance for diagnosis and monitoring disease course. MATERIALS AND METHODS: We retrospectively identified 98 inpatients in a general ward at Kashiwa Municipal Hospital from May 1st, 2020, to October 31st, 2020. We extracted data on patient demographics, symptoms, comorbidities, blood test results, radiographic findings, treatment after admission and clinical course. We compared clinical findings between patients with and without atypical lymphocytes, investigated the behavior of atypical lymphocytes throughout the clinical course of COVID-19, and determined the relationships among the development of pneumonia, the use of supplemental oxygen and the presence of atypical lymphocytes. RESULTS: Patients with atypical lymphocytes had a significantly higher prevalence of pneumonia (80.4% vs. 42.6%, p < 0.0001) and the use of supplemental oxygen (25.5% vs. 4.3%, p = 0.0042). The median time to the appearance of atypical lymphocytes after disease onset was eight days, and atypical lymphocytes were observed in 16/98 (16.3%) patients at the first visit. Atypical lymphocytes appeared after the confirmation of lung infiltrates in 31/41 (75.6%) patients. Of the 13 oxygen-treated patients with atypical lymphocytes, approximately two-thirds had a stable or improved clinical course after the appearance of atypical lymphocytes. CONCLUSION: Atypical lymphocytes frequently appeared in the peripheral blood of COVID-19 patients one week after disease onset. Patients with atypical lymphocytes were more likely to have pneumonia and to need supplemental oxygen; however, two-thirds of them showed clinical improvement after the appearance of atypical lymphocytes.

Development of Robotic Rollators and Walking Trolleys in Japan.

In Japan, several types of robotic rollators and walking trolleys have been developed with financial assistance from the Japanese government, and some of them have been commercialized in 2015 and 2016. In this paper, the specifications and features of these devices are presented. Moreover, the physically assistive effects of these devices in elderly users are verified and discussed using the results of fundamental function tests and verification experiments.

Development of a Risk Assessment Assistance Tool for Robotic Care Devices.

Aiming to eliminate a labor shortage caused by the aging of society, many kinds of service robots are under development. Nursing care for the elderly is considered as a typical application of service robots, especially in Japan. Elderly care robots or robotic care device must be designed with safety, but not a few manufacturers are inexperienced in designing and manufacturing them on the basis of safety. In this paper, we introduce a risk assessment assistance tool for robotic care device targeted for inexperienced manufacturers of risk assessment.

Expression, purification, crystallization and preliminary crystallographic analysis of hepatitis B virus core protein dimerized via a peptide linker containing an EGFP insertion.

Virus-like particles (VLPs) have many potentially useful applications. The core proteins of human hepatitis B virus self-assemble into icosahedral VLPs. As previously reported, core protein dimers (CPDs), produced by connecting two core proteins via a peptide linker, can also assemble into VLPs. CPDs in which heterologous proteins were connected to the C-terminus (CPD1) were found to rearrange into symmetrical octahedra during crystallization. In this study, a heterologous protein was inserted into the peptide linker of the CPD (CPD2). CPD2 was expressed in Escherichia coli, assembled into VLPs, purified and crystallized. A single crystal diffracted to 2.8 Å resolution and belonged to the cubic space group F432, with unit-cell parameters a = b = c = 218.6 Å. Single-crystal analysis showed that CPD1 and CPD2 rearranged into the same octahedral organization in a crystallization solution.

Emerging superconductivity hidden beneath charge-transfer insulators.

In many of today's most interesting materials, strong interactions prevail upon the magnetic moments, the electrons, and the crystal lattice, forming strong links between these different aspects of the system. Particularly, in two-dimensional cuprates, where copper is either five- or six-fold coordinated, superconductivity is commonly induced by chemical doping which is deemed to be mandatory by destruction of long-range antiferromagnetic order of 3d(9) Cu(2+) moments. Here we show that superconductivity can be induced in Pr2CuO4, where copper is four-fold coordinated. We induced this novel quantum state of Pr2CuO4 by realizing pristine square-planar coordinated copper in the copper-oxygen planes, thus, resulting in critical superconducting temperatures even higher than by chemical doping. Our results demonstrate new degrees of freedom, i.e., coordination of copper, for the manipulation of magnetic and superconducting order parameters in quantum materials.

Expression, purification, crystallization and preliminary X-ray crystallographic studies of hepatitis B virus core fusion protein corresponding to octahedral particles.

Recombinant hepatitis B virus core proteins dimerize to form building blocks that are capable of self-assembly into a capsid. A core capsid protein dimer (CPD) linked to a green fluorescent protein variant, EGFP, at the C-terminus has been designed. The recombinant fusion CPD was expressed in Escherichia coli, assembled into virus-like particles (VLPs), purified and crystallized. The single crystal diffracted to 2.15 Å resolution and belonged to the cubic space group F432, with unit-cell parameters a = b = c = 219.7 Å. The fusion proteins assembled into icosahedral VLPs in aqueous solution, but were rearranged into octahedral symmetry through the crystal-packing process under the crystallization conditions.

Combination chemotherapy with weekly paclitaxel or docetaxel, carboplatin, and estramustine for hormone-refractory prostate cancer.

Paclitaxel (PTX) and docetaxel (DTX) have been reported to be effective for treating hormone-refractory prostate cancer (HRPC). The objective of this study was to examine the efficacy of weekly DTX (PTX)-based chemotherapy and compare weekly DTX-based chemotherapy with triweekly (once every 3 weeks) DTX-based chemotherapy. We performed a combination chemotherapy on a weekly cycle with an i.v. PTX 100 mg/m(2) or i.v. DTX 30 mg/m(2) (days 1, 8, 15, and 22), i.v. carboplatin (CBDCA) (day 1, area under the plasma concentration time curve = 6), and oral estramustine phosphate 10 mg/kg daily for 10 HRPC patients. In addition, we investigated the patient characteristics and treatment efficacy and toxicity. Among all cases, serum prostate-specific antigen (PSA) decreased by 50% or more in 90% of patients, by 75% or more in 70%, and 90% or more in 40% after chemotherapy. The effectiveness of weekly DTX-based chemotherapy was comparable with previous reports, and we showed no toxicity serious enough to require cancellation of chemotherapy. In conclusion, weekly DTX-based chemotherapy was no less effective and less toxic than triweekly DTX-based chemotherapy for HRPC patients and therefore can be useful as the first-line chemotherapy regimen for HRPC patients, especially the elderly or those with a poor performance status.

[Carcinomatous meningitis from prostate cancer diagnosed by cerebrospinal fluid cytology and magnetic resonance image: a case report and review of the literature].

A 55-year-old man was treated with 10 courses of intermittent Paclitaxel, estramustine phosphate sodium and carboplatin (PEC) chemotherapy for hormone-refractory prostate cancer. He was admitted to our department with a complaint of severe headache 2 years after initiating chemotherapy. Enhanced computed tomography (CT) of the brain demonstrated no obvious lesion, but a brain dynamic magnetic resonance image (MRI) showed a diffusely enhanced lesion on the surface of the brain. Cerebrospinal fluid cytology revealed adenocarcinoma cells; and therefore it was diagnosed as carcinomatous meningitis metastasized from prostate cancer. After glycerin and betamethasone were used to control brain edema, the patient's headache temporarily improved. However, he died on the 36th day after admission in the natural course of the disease after he and his family selected not to undertake further active treatment. To our knowledge, only 6 cases of carcinomatous meningitis associated with prostate cancer have been reported in Japan. It is generally difficult to diagnose carcinomatous meningitis because the symptoms vary considerably. Once diagnosed, active treatment is not undertaken in most cases since the patient cannot tolerate further treatment. The prognoses for patients with advanced prostate cancer and metastatic carcinomatous meningitis are generally quite poor. Early diagnosis and prompt initiation of therapy could improve the quality of life for such patients. In this case study, MRI was superior to CT for imaging a metastatic carcinomatous meningitis lesion.

[Traumatic urethral disruption treated by endoscopic management with transluminal puncture under fluoroscopic guidance: a case report and review of the literature].

A 76-year-old man injured in a car accident was admitted with urinary retention and urethral bleeding. Cystoscopic findings revealed disruption of the bulbous urethra and we performed cystostomy. At sixty days after the injury, we performed endoscopic urethroplasty with a steel needle puncturing from the proximal end of the disruption to the distal end under the guidance of C-Arm fluoroscopy. We removed the urethral catheter at the 37th day after surgery and then performed urethral dilation for postoperative urethral stricture. Retrograde urethrocystography showed no urethral stricture at 5 months after surgery. The patient had no dysuria or urinary incontinence. Endoscopic urethroplasty generally needs some guiding device to perform urethrotomy. C-Arm fluoroscopy and transluminal puncture were used in this case and proved useful for guidance from the proximal to the distal end of the urethral disruption. In particular, three dimensional imaging could demonstrate clearly the direction of the needle, making it easier to perform endoscopic urethroplastic surgery safely. Endoscopic urethroplasty which is minimally invasive for patients can be performed with shorter operating time and less blood loss than open surgery by urologists used to endoscopic treatment. Endoscopic surgery can be useful for selected patients of advanced age, in poor general condition, or with severe complications.

Field evaluation of spatial repellency of metofluthrin-impregnated plastic strips against Anopheles gambiae complex in Bagamoyo, coastal Tanzania.

Metofluthrin is a newly synthesized pyrethroid possessing high knockdown and lethal activity against mosquitoes. Studies of metofluthrin-impregnated plastic strips have been performed with dengue vectors. This study reports the efficacy of the new prototypes of metofluthrin-impregnated plastic strips against malaria vectors, Anopheles gambiae complex, in the Kongo villages of Bagamoyo district in coastal Tanzania. The study, using 20 houses, half intervention, half control, was conducted for a 124-day period. Pyrethrum spray sheets and Centers for Disease Control and Prevention light traps were used to sample mosquito population indices. The mosquito density indices of the intervention houses were observed to be significantly lower than those of the control houses when pyrethrum spray sheet collection was used (F = 4.61, 1 df, P = 0.038; 98.7% reduction of total mosquito collection compared with that for the controls). These low indices were observed despite the large openings found in Bagamoyo houses, which were predicted to have a considerable negative effect on the spatial repellency of metofluthrin. Based on the present results, the pyrethrum spray sheet collection was the better of the 2 collection methods.

213 W average power of 2.4 GW pulsed thermally controlled Nd:glass zigzag slab laser with a stimulated Brillouin scattering mirror.

We report a high-average-power and high-pulse-energy diode-pumped Nd:glass laser amplifier system consisting of two thermally-edge-controlled zigzag slab amplifiers and a stimulated Brillouin scattering mirror. This phase-conjugated system produces an average power of 213 W at 10 Hz in a 8.9 ns pulse (2.4 GW peak power) with an optical-to-optical conversion efficiency of 11.7% and a near-diffraction-limited beam. To the best of our knowledge, this is the highest performance from a Nd:glass-based laser amplifier system ever built.

NMR structure of an intracellular third loop peptide of human GABA(B) receptor.

GABA(B) receptor is a G protein-coupled receptor for GABA and drug target for neurological and psychiatric disorders. From the analysis of GTPgammaS binding assay, we found that a synthesized peptide (GABAb: ETKSVSTEKINDHR) corresponding to the intracellular third loop region of metabotropic GABA(B) receptor could activate G(i) protein alpha subunit directly. The three dimensional molecular structure of the peptide in SDS-d(25) micelles was determined by 2D (1)H-NMR spectroscopy. GABAb peptide formed an alpha helical structure and a positive charge cluster at the C-terminal site. These structural features were also found in several other G protein activating peptides. From the comparison among these peptides, we found that peptides with high helical content show the high activity.

NMR structure of a human homologous methuselah gene receptor peptide.

Human APG1 gene is homologous to Drosophila methuselah gene associated with extended life span. A peptide (APG1: RNGKRSNRTLREE) corresponding to a predicted region of the intracellular third loop of G protein-coupled receptor coded in human APG1 gene could activate Gi protein alpha subunit directly. The three-dimensional molecular structure of the peptide in SDS-d25 micelles was determined by 2D 1H NMR spectroscopy. APG1 formed an alpha-helical structure at the C-terminal site and a positive charge cluster at the N-terminal site. The cluster was also found in several other Gi protein-coupled receptor peptides. Therefore, the positive charge cluster on the helical structure might be engaged in G protein activation.

Quantification of the number of EP3 receptors on a living CHO cell surface by the AFM.

The distribution of EP3 receptors on a living cell surface was quantitatively studied by atomic force microscopy (AFM). Green fluorescent protein (GFP) was introduced to the extracellular region of the EP3 receptor on a CHO cell. A microbead was used as a probe to ensure certain contact area, whose surface was coated with anti-GFP antibody. The interactions between the antibodies and GFP molecules on the cell surface were recorded to observe the distribution of the receptors. The result indicated that EP3 receptors were distributed on the CHO cell surface not uniformly but in small patches coincident with immunohistochemical observation. Repeated measurements on the same area of cell surface gave confirmation that it was unlikely that the receptors were extracted from the cell membrane during the experiments. The measurement of single molecular interaction between GFP and the anti-GFP antibody was succeeded on the cell surface using compression-free force spectroscopy. The value of separation work required to break a single molecular pair was estimated to be about 1.5 x 10(-18)J. The number of EP3 receptor on the CHO cell surface was estimated using this value to be about 1 x 10(4) under the assumption that the area of the cell surface was about 5,000 microm(2). These results indicated that the number of receptors on a living cell surface could be quantified through the force measurement by the AFM.

NMR structure of an intracellular loop peptide derived from prostaglandin EP3alpha receptor.

We found that a peptide (EP3a: TIKALVSRCRAKAAV) corresponding to the N-terminal site of the intracellular third loop of human prostaglandin EP3alpha receptor could activate G protein alpha-subunit directly. The activity was almost same as Mastoparan-X, a G protein activating peptide from wasp venom. The three-dimensional molecular structure of the peptide in SDS-d(25) micelles was determined by 2D (1)H NMR spectroscopy. The structure of EP3a consists of a positive charge cluster on the C-terminal helical site. The cluster was also found in several corresponding receptor peptides. Therefore, the positive charge cluster on the helical structure might play a crucial role in activation of G protein.

Interaction between amyloid beta-protein aggregates and membranes.

The conversion of soluble, nontoxic amyloid beta-protein (Abeta) to aggregated, toxic Abeta rich in beta-sheet structures is considered to be the key step in the development of Alzheimer's disease. Therefore, extensive studies have been carried out on the mechanisms involved in Abeta aggregation and the characterization of Abeta aggregates formed in aqueous solutions mimicking biological fluids. On the other hand, several investigators pointed out that membranes play an important role in Abeta aggregation. However, it remains unclear whether Abeta aggregates formed in solution and membranes are identical and whether the former can bind to membranes. In this study, using a dye-labeled Abeta-(1-40) as well as native Abeta-(1-40), the properties of Abeta aggregates formed in buffer and raft-like membranes composed of monosialoganglioside GM1/cholesterol/sphingomyelin were compared. Fourier transform infrared spectroscopic measurements suggested that Abeta aggregates formed in buffer and in membranes have different beta-sheet structures. Fluorescence experiments revealed that Abeta aggregated in buffer did not show any affinity for membranes.

Crystallization and preliminary X-ray diffraction studies of DNA decamer d(CCAGGCCTGG) complexed with cobalt(III)-pepleomycin.

Crystals of the self-complementary oligonucleotide d(CCAGGCCTGG) [Heinemann & Alings (1989), J. Mol. Biol. 210, 369-381] complexed with the hydroperoxide of cobalt-pepleomycin (CoPEP) were obtained by the hanging-drop vapour-diffusion method at 298 K. An X-ray diffraction data set was collected to 2.8 A at 100 K. The crystal belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 34.52, b = 59.88, c = 72.93 A.

MgATP-induced conformational changes in a single myosin molecule observed by atomic force microscopy: periodicity of substructures in myosin rods.

This paper discusses the conformational changes in a single myosin molecule directly observed using atomic force microscopy (AFM). The myosin molecules were pretreated in rigor solutions without MgATP or in relaxed solutions with various concentrations of MgATP. The images of these molecules were obtained using a tapping mode AFM. The results indicate that the orientation of the myosin's heads and tail strongly depend on the MgATP concentration. Without using MgATP, almost all of the myosin molecules are in the extended form; however, when MgATP is used, the molecules bend according to the level of MgATP concentration. The mean-square end-to-end distance of the myosin molecules is significantly shorter with p[MgATP] = 4 than with p[MgATP] = 6. The rod region did not show the same level of intensity along their length in the extended form. The rods exhibited clusters of discontinuity, which were identified as substructures. The size of these substructures change at intervals that are multiples of 14.3-14.5 nm, which reflects the periodicity of the alpha-helical coiled coils. The substructure clusters also correspond to the myosin crossbridge spacing in muscles (14.3 or 43 nm). These results suggest that the myosin's head bends in conjunction with the bending or tilting in the helical substructures. Conformational changes of the myosin molecule induced by MgATP seem to mimic the molecular motions in a muscle's force generation process.

Surgical management of the urinary tract in patients with locally advanced colorectal cancer.

OBJECTIVES: To review cases of colorectal cancer requiring urologic management to clarify the role the urologist should play in the surgical procedures. A deterrent to radical surgery for advanced colorectal carcinoma with urinary involvement is the technical complexity and associated morbidity and mortality of this procedure. METHODS: Thirty-six tumors in 35 patients, including 19 sigmoid cancers (Stage II, 17; Stage III, 2), 12 rectal cancers (Stage II, 11; Stage III, 1), and 5 local recurrences of colorectal carcinoma in the pelvis were reviewed. All tumors had invaded the bladder, prostate, or ureter. The demographic and clinical characteristics, type of operative procedure, and postoperative complications were analyzed. RESULTS: Of the patients with a sigmoid tumor, partial cystectomy was performed in 15 patients who underwent a bladder-sparing procedure; an ileal conduit and ileal neobladder were created in 2 patients each who required cystectomy. Four patients with rectal cancer underwent a bladder-sparing procedure: partial cystectomy in 1, partial cystectomy with ileal ureter in 1, and prostatectomy in 2. The remaining 8 patients underwent cystectomy with the following types of reconstruction: colonic neobladder in 1, ileal neobladder in 4, Indiana pouch in 1, ileal conduit in 1, and ureterocutaneostomy in 1 patient. The bladder was spared in a greater percentage of patients with sigmoid cancer than in those with rectal cancer. The incidence of complications was greater in patients with rectal cancer and local recurrence than in those with sigmoid tumors. The complication rate was especially low in patients who underwent a bladder-sparing procedure (10.5%) compared with patients who required cystectomy (58.3%). The survival in patients with sigmoid cancer who underwent bladder-sparing surgery also was better than in those who underwent cystectomy. CONCLUSIONS: The treatment of advanced colorectal cancer is best managed by a committed team that includes an experienced urologist. Urologists play a critical role in determining the surgical options and creating appropriate urinary diversions to achieve curative resection with the highest quality of life.