Unique morphological architecture of the hamstring muscles and its functional relevance revealed by analysis of isolated muscle specimens and quantification of structural parameters.

The structural and functional differences of individual hamstrings have not been sufficiently evaluated. This study aimed to clarify the morphological architecture of the hamstrings including the superficial tendons in detail using isolated muscle specimens, together with quantification of structural parameters of the muscle. Sixteen lower limbs of human cadavers were used in this study. The semimembranosus (SM), semitendinosus (ST), biceps femoris long head (BFlh), and biceps femoris short head (BFsh) were dissected from cadavers to prepare isolated muscle specimens. Structural parameters, including muscle volume, muscle length, fiber length, sarcomere length, pennation angle, and physiological cross-sectional area (PCSA) were measured. In addition, the proximal and distal attachment areas of the muscle fibers were measured, and the proximal/distal area ratio was calculated. The SM, ST, and BFlh were spindle-shaped with the superficial origin and insertion tendons on the muscle surface, and the BFsh was quadrate with direct attachment to the skeleton and BFlh tendon. The muscle architecture was pennate in the four muscles. The four hamstrings possessed either of two types of structural parameters, one with shorter fiber length and larger PCSA, as in the SM and BFlh, and the other with longer fiber length and smaller PCSA, as in the ST and BFsh. Sarcomere length was unique in each of the four hamstrings, and thus the fiber length was suitably normalized using the average sarcomere length for each, instead of uniform length of 2.7 µm. The proximal/distal area ratio was even in the SM, large in the ST, and small in the BFsh and BFlh. This study clarified that the superficial origin and insertion tendons are critical determinants of the unique internal structure and structural parameters representing the functional properties of the hamstring muscles.

A nationwide cross-sectional study using a web-based questionnaire survey of the duration of isolation of COVID-19 inpatients with cancer at Japanese cancer centers.

There is no clear consensus regarding the optimal isolation duration for immunocompromised patients with coronavirus disease 2019 (COVID-19). Therefore, we conducted a questionnaire survey at eight Japanese cancer centers to investigate the practices of infectious disease specialists regarding the duration of isolation for COVID-19 inpatients with cancer. For asymptomatic to severely ill COVID-19 inpatients without severe immunodeficiency, four centers reported at least 10 days of isolation without testing, and two reported at least 20 days. Two centers incorporated polymerase chain reaction (PCR) as a criterion for terminating the isolation of inpatients without severe immunodeficiency. For severely immunocompromised COVID-19 inpatients, at least 20 days of isolation were required in seven facilities, regardless of illness severity. Additionally, seven centers had implemented Ct or antigen quantification test values as criteria for de-isolating severely immunocompromised inpatients. No cases caused nosocomial outbreaks after isolation was terminated based on each facility's criteria for isolation termination. Thus, cancer patients required longer isolation periods than the general population in most facilities, and for those with severe immunodeficiency, the isolation periods were longer and more tightly controlled with tests.

Fecal Microbes Associated with the Outcomes After Esophagectomy in Patients with Esophageal Cancer.

BACKGROUND: Although accumulating evidence suggests that an imbalanced gut microbiota leads to cancer progression, few studies demonstrated the implication in patients who underwent oncologic esophagectomy. This study aimed to elucidate the association between gut microbes and the outcomes after oncologic esophagectomy, as well as the host's inflammatory/nutritional status. METHODS: Overall, 783 consecutive patients who underwent oncologic esophagectomy were eligible. We investigated the microbiota detected by fecal culture tests and then assessed the association between the gut microbiota and patient characteristics, short-term outcomes, and long-term survival. RESULTS: Seventeen different species could be cultivated. We comprehensively examined the impact of each detected microbe on survival. The presence of Bacillus species (Bacillus sp.; 26.8%) was associated with favorable prognosis on overall and cancer-specific survival (p = 0.02 and 0.02, respectively). Conversely, the presence of Proteus mirabilis (P. mirabilis; 3.4%) was associated with unfavorable overall and recurrence-free survivals (p = 0.02 and < 0.01, respectively). Multivariate analysis showed that the presence of P. mirabilis was one of the independent prognostic factors for poor recurrence-free survival (p < 0.01). Patients with Bacillus sp. had lower modified Glasgow prognostic score and better response to preoperative treatment than those without (p = 0.01 and 0.03, respectively). Meanwhile, patients with P. mirabilis were significantly associated with higher systemic inflammation scores and increased postoperative pneumonia incidence than those without (p = 0.01 and 0.02, respectively). CONCLUSIONS: Preoperative fecal microbiota was associated with the host's inflammatory and nutritional status and may influence the outcomes after oncologic esophagectomy.

Clinical characteristics and risk factors associated with Pneumocystis jirovecii infection in patients with solid tumors: study of thirteen-year medical records of a large cancer center.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP)-related risk factors among patients with solid tumors are not completely defined. Thus, we aimed to characterize PCP cases with underlying solid tumors, to highlight the factors contributing to its development besides the prolonged use of moderate-to-high dose corticosteroids. METHODS: We retrospectively reviewed the medical records of patients with solid tumors diagnosed with PCP between 2006 and 2018 at a cancer center in Tokyo, Japan. Demographic and clinical data were collected, which included malignancy types, total lymphocyte count, coexisting pulmonary disease, chemotherapy, radiation therapy, corticosteroid use, and PCP-attributable mortality. RESULTS: Twenty cases of PCP with solid tumors were documented in 151,718 patients and 788,914 patient-years. Lung cancer (n = 6, 30%) was the most common underlying tumor, followed by breast cancer (n = 3, 15%). Only six (30%) patients were taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks from the onset of PCP. Among the remaining 14 patients, seven (50%) had coexisting pulmonary diseases, 10 (71%) had received chemotherapy within 90 days prior to PCP diagnosis, seven (50%) had undergone chest radiation therapy before PCP diagnosis, seven (50%) had received only intermittent corticosteroids, and one (7%) received no corticosteroids. Mortality attributable to PCP was 40%. CONCLUSIONS: More than half of the patients were not taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks. Multiple other factors (e.g., lymphocytopenia, radiation to chest) may have potentially contributed to PCP in patients with solid tumors in a composite manner. We need to establish a method for estimating the likelihood of PCP taking multiple factors into account in this patient population.

[DRUG-INDUCED LUPUS CAUSED BY LONG TERM MINOCYCLINE TREATMENT FOR ACNE VULGARIS].

An 18-year-old Japanese girl had received oral minocycline 200mg daily for treatment of acne vulgaris since 16 years old. She had a fever three months before admission, followed by joint pains in her knees, elbows and several proximal interphalangeal joints one month before admission. She was referred to our hospital because of a high serum level of anti-DNA antibody. She had already discontinued oral minocycline five weeks before admission, because she missed her medication refilled. On admission, the arthralgia and fever spontaneously resolved, and there were no laboratory evidence of hypocomplementemia and cytopenia. She had neither erythema nor internal organ involvements. Because her symptoms subsided spontaneously after the cessation of minocycline, she was considered to have drug-induced lupus. Both the arthralgia and fever did not relapse, and anti-ds DNA antibody returned to normal during a follow-up period without treatment. There are few reports of drug-induced lupus caused by minocycline in Japan. This case highlights the importance of considering minocycline-induced lupus.

Maltopentaose-conjugated CTA for RAFT polymerization generating nanostructured bioresource-block copolymer.

We now describe the synthesis of a new family of oligosaccharide-conjugated functional molecules, which act as chain transfer agents (CTAs) for the reversible addition-fragmentation chain transfer (RAFT) polymerization. The synthesis was started from the catalyst-free direct N-glycosyl reaction of 5-azidopentylamine onto maltopentaose (Mal5) in dry methanol at room temperature and subsequent N-protected reaction with acetic anhydride, producing a stable oligosaccharide-building block, such as Mal5 with an azidopentyl group (Mal5-N3). The azido group was hydrogenated using platinum dioxide (PtO2) as a catalyst to give Mal5 with aminopentyl group (Mal5-NH2), which was then reacted with CTA molecules bearing activated ester moieties. These reactions produced Mal5-modified macro-CTAs (Mal5-CTAs, 1), which were used for the RAFT polymerizations of styrene (St) and methyl methacrylate (MMA) in DMF. The polymerizations were performed using the [M]0/[1]0 values ranging from 50 to 600, affording the Mal5-hybrid amphiphilic block copolymers (BCPs), such as Mal5-polystyrene (2) and Mal5-poly(methyl methacrylate) (3), with a quantitative end-functionality and the controlled molecular weights between 4310 and 20 300 g mol(-1). The small-angle X-ray scattering (SAXS) measurements were accomplished for 2 and 3 to ensure their abilities to form phase separated structures in their bulk states with the increasing temperatures from 30 to 190 °C. The featured results were observed for 2 (ϕMal5 = 0.14) and 3 (ϕMal5 = 0.16) at temperatures above 100 °C, where ϕMal5 denotes the volume fraction of the Mal5 unit in the BCP sample. For both BCP samples, the primary scattering peaks q* were clearly observed together with the higher-ordered scattering peaks √2q* and √3q*. Thus, these Mal5-hybrid amphiphilic BCP samples have a body centered cubic (BCC) phase morphology. The domain spacing (d) values of the BCC morphology for 2 (ϕMal5 = 0.14) and 3 (ϕMal5 = 0.16) were 10.4 and 9.55 nm, respectively, which were determined using Bragg's relation (d = 2π/q*). The present RAFT agents were shown to eventually provide the phase separated structural polymeric materials in which 5.4 nm bioresource-spherical domains were periodically arrayed at the interval of about 10 nm.

A display of pH-sensitive fusogenic GALA peptide facilitates endosomal escape from a Bio-nanocapsule via an endocytic uptake pathway.

BACKGROUND: An affibody-displaying bio-nanocapsule (ZHER2-BNC) with a hepatocyte specificity derived from hepatitis B virus (HBV) was converted into an affibody, ZHER2, that recognizes HER2 receptors. This affibody was previously reported to be the result of the endocytosis-dependent specific uptake of proteins and siRNA into target cancer cells. To assist the endosomal escape of inclusions, a helper lipid with pH-sensitive fusogenic ability (1,2-dioleoyl-sn-glycero-3-phos phoethanolamine; DOPE) was conjugated with a ZHER2-BNC. FINDINGS: In this study, we displayed a pH-sensitive fusogenic GALA peptide on the surface of a particle in order to confer the ability of endosomal escape to a ZHER2-BNC. A GALA-displaying ZHER2-BNC purified from yeast uneventfully formed a particle structure. Furthermore, endosomal escape of the particle was facilitated after endocytic uptake and release of the inclusions to the cytoplasm without the cell toxicity. CONCLUSION: The genetic fusion of a GALA peptide to the virus-like particle confers the ability of endosomal escape.

Outbreak of Streptococcus pyogenes emm89 ST646 in a head and neck surgical oncology ward.

Streptococcus pyogenes causes a variety of human infections, and hospital outbreaks with this pathogen have also been reported. The purpose of this study is to describe the clinical characteristics of an outbreak of S. pyogenes involving 15 patients and four healthcare workers (HCWs), as well as the molecular characteristics of the causative isolates. The course and response to the outbreak were reviewed, and information on the characteristics of the patients was extracted retrospectively from the medical records. Whole-genome sequencing of the 16 causative isolates (14 from patients and two from HCWs) was also performed. All 15 patients were postoperative of head and neck cancer with tracheotomy, and 12 had invasive infections, primarily surgical site infections, all of which resolved without causing serious illness. All but the first case was detected more than 7 days after admission. S. pyogenes was detected in two patients after empiric antimicrobial administration was performed on all inpatients and HCWs, and the outbreak was finally contained in approximately 2 months. All isolates detected in patients and HCWs belonged to emm89/clade 3, a hypervirulent clone that has emerged worldwide and was classified as sequence type 646. These isolates had single nucleotide polymorphism (SNP) differences of zero to one, indicating clonal transmission. This study demonstrated an outbreak of S. pyogenes emm89/clade 3 in a ward of patients with head and neck cancer. The global emergence of hypervirulent isolates may increase the risk of outbreaks among high-risk patients. IMPORTANCE: This study describes an outbreak of Streptococcus pyogenes that occurred in a ward caring for patients with head and neck cancer and tracheostomies. Many cases of invasive infections occurred in a short period, and extensive empiric antimicrobial administration on patients and healthcare workers was performed to control the outbreak. Whole-genome sequencing analysis of the causative strains confirmed that it was a monoclonal transmission of strains belonging to emm89/clade 3. The epidemiology and clinical characteristics of S. pyogenes infections have changed with the replacement of the prevalent clones worldwide. In the 1980s, there was a reemergence of S. pyogenes infections in high-income countries due to the spread of hypervirulent emm1 strains. emm89/clade 3 has recently been spreading worldwide and shares common features with emm1, including increased production of two toxins, NADase, and streptolysin O. The outbreak reported here may reflect the high spreading potential and virulence of emm89/clade 3.

A case of subacute infective endocarditis and blood access infection caused by Enterococcus durans.

BACKGROUND: Infection by Enterococcus durans (E. durans) is very rare; reported cases are often preceded by therapy or an immunosuppressed state, including infective endocarditis, urinary tract infection, or wound infection. A few reported cases of infective endocarditis exist, with no reports describing involvement of blood access infection. CASE PRESENTATION: The patient is an 83-year-old man who had been undergoing hemodialysis for 8 years due to renal failure caused by diabetic nephropathy. He developed infective endocarditis and blood access infection/infective aneurysm due to Enterococcus durans; these conditions were treated with the antibiotic regimen of ampicillin + gentamicin. There have been only a few reported cases of infective endocarditis caused by E. durans, and to our knowledge, this is the first report of blood access infection. CONCLUSIONS: We have experienced a case of concurrent infective endocarditis and blood access infection/infective aneurysm caused by E. durans. This is the world's first reported case of blood access infection/infective aneurysm by E. durans.

Antimicrobial susceptibility and penicillin-binding protein 1 and 2 mutations in Neisseria gonorrhoeae isolated from male urethritis in Sapporo, Japan.

The spread of antimicrobial-resistant Neisseria gonorrhoeae worldwide is a critical issue in the control of sexually transmitted infections. The purpose of this study was to clarify recent trends in the susceptibility of N. gonorrhoeae to various antimicrobial agents and to compare these data with our previous data. Minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined in N. gonorrhoeae strains clinically isolated from male gonococcal urethritis. In addition, amino acid sequencing of penicillin-binding protein (PBP) 2, encoded by the penA gene, was analyzed so that genetic analysis of mosaic PBP 2 could clarify the susceptibility of the strains to cefixime and other cephalosporins. The susceptibility rate for ceftriaxone, cefodizime, and spectinomycin, agents whose use is recommended by the guideline of the Japanese Society of Sexually Transmitted Infections (JSSTI), was 100 %. The susceptibility rates of the strains to penicillin G and ciprofloxacin were lower than those in previous reports. Mosaic PBP 2 structures were detected in 51.9 % of the strains and the MICs of the strains with the mosaic PBP 2 to cefixime were much higher than those of the strains without the mosaic PBP 2. In the clinical situation, the treatment regimen recommended by the JSSTI remains appropriate; however, the susceptibility to cephalosporins should be intensively surveyed because strains with mosaic PBP 2 were commonly detected.

Clinical efficacy of sitafloxacin 100 mg twice daily for 7 days for patients with non-gonococcal urethritis.

To clarify the clinical efficacy of STFX for patients with non-gonococcal urethritis (NGU), including chlamydial urethritis and Mycoplasma genitalium-positive urethritis, this study included male patients with NGU who were 20 years old or older. The pathogens, including Chlamydia trachomatis, M. genitalium and Ureaplasma urealyticum, were detected by nucleic acid amplification tests and the patients were treated with sitafloxacin 100 mg twice daily for 7 days. Microbiological and clinical efficacies were assessed for the patients with NGU posttreatment. Among the 208 patients enrolled in this study, data for a total of 118 patients could be analyzed. The median age was 32 (20-61) years. The median duration from the completion of treatment to the second visit was 21 (14-42) days. There were 68 pathogen-positive NGU cases and 50 with NGU without any microbial detection. Microbiological cure was achieved in 95.6% of the pathogen-positive NGU patients. Total clinical cure was achieved in 91.3% (105/115). In this study, STFX was able to eradicate 95.7% of C. trachomatis, 93.8% of M. genitalium and 100% of U. urealyticum. The results of our clinical research indicate that the STFX treatment regimen should become a standard regimen recommended for patients with NGU. In addition, this regimen is recommended for patients with M. genitalium-positive NGU.

Acute effect of short-term immobilization on lower leg muscle tissue hardness in healthy adults.

BACKGROUND: Previous studies have reported altered neural activity in the motor cortex after short-term cast immobilization, even in healthy participants. However, the effects of short-term movement restriction on tissue structure are not well understood. OBJECTIVE: To investigate the effects of short-term lower limb immobilization on muscle tissue hardness. METHODS: Seventeen healthy participants were enrolled in the study. Each participant's non-dominant lower limb was fixed with a soft bandage and medical splint for 10 h. Gastrocnemius muscle tissue hardness was measured using a tissue hardness meter before cast application and immediately after cast removal. Measurements were performed five times for each lower limb, and the three values with the lowest coefficient of variance were adopted as the value of muscle tissue hardness. RESULTS: Gastrocnemius muscle tissue hardness in the immobilized limb was lower after cast removal than that before cast application (from 53.6 to 51.8; p< 0.01), whereas the non-fixed limb showed an increase in muscle tissue hardness at the end of the experiment (from 52.9 to 54.3; p= 0.03). CONCLUSION: The findings indicate that 10 h movement restriction induced a reduction in muscle tissue hardness, suggesting acute adverse effects of cast immobilization for orthopedic treatment.

Myocarditis associated with immune-checkpoint inhibitors diagnosed by cardiac magnetic resonance imaging.

Myocarditis associated with immune-checkpoint inhibitors (ICIs) is a rare, but critical adverse event. Although endomyocardial biopsy (EMB) is the standard for diagnosis of myocarditis, there is a possibility of false negatives due to sampling errors and local nonavailability of EMB, which may hamper the appropriate diagnosis of myocarditis. Therefore, an alternative criterion based on cardiac magnetic resonance imaging (CMRI) combined with clinical presentation has been proposed, but not emphasized sufficiently. We report a case of myocarditis after ICIs administration, which was diagnosed using CMRI in a 48-year-old male with lung adenocarcinoma. CMRI provides an opportunity to diagnose myocarditis during cancer treatment.

Comparison of the Treatment Outcome of Piperacillin-Tazobactam versus Carbapenems for Patients with Bacteremia Caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli in Areas with Low Frequency of Coproduction of OXA-1: a Preliminary Analysis.

Although piperacillin-tazobactam (TZP) was shown to be less effective than carbapenems in treating bacteremia due to extended-spectrum ß-lactamase-producing (ESBL)-producing organisms in a randomized controlled trial, the fact that many of the causative organisms co-produced inhibitor-resistant OXA-1 along with ESBLs may have influenced the results. In this study, we compared the therapeutic effectiveness of TZP and carbapenem in treating ESBL-producing Escherichia coli bacteremia in areas with low frequency of OXA-1 co-production. Forty patients, 14 in the TZP treatment group and 26 in the carbapenem treatment group, were included in the analysis. There were no significant differences in patient background between the two groups. Urinary tract infection or cholangitis was the source of bacteremia in 26 patients (65%), and the Pitt bacteremia score was zero or one in 35 patients (87.5%). Only four (11.4%) of the 35 causative isolates available for microbiological analysis harbored blaOXA-1, and only three (8.6%) were non-susceptible to TZP. Seventeen (48.6%) isolates carried blaCTX-M-27, none of which carried other ß-lactamase genes. No significant difference in the frequency of treatment failure on day 14 of bacteremia was documented between the TZP and carbapenem treatment groups in both the crude analysis and the inverse probability of treatment weighting-adjusted analysis. This study demonstrates that TZP may be a treatment option for non-severe cases of ESBL-producing E. coli bacteremia in areas with low frequency of OXA-1 co-production. IMPORTANCE Although carbapenems are considered the drug of choice for severe infections caused by extended-spectrum ß-lactamase-producing (ESBL)-producing organisms, other therapeutic options are being explored to avoid increasing the selective pressure for carbapenem-resistant organisms. In this study, it was suggested that piperacillin-tazobactam may be as effective as carbapenems for the treatment of mild bacteremia caused by ESBL-producing Escherichia coli in areas where OXA-1 co-production by ESBL-producing E. coli is rare. The genetic background of each regional epidemic clone differs even among multidrug-resistant bacteria classified under the same name (e.g., ESBL-producing organisms), resulting in possible differences in the efficacy of therapeutic agents. Exploration of treatment options for multidrug-resistant organisms according to local epidemiology is worthwhile from the perspective of antimicrobial stewardship.

Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis.

To confirm the efficacy of the treatment regimen with oral levofloxacin (LVFX) 500 mg once daily for 7 days for patients with non-gonococcal urethritis (NGU), we evaluated the microbiological and clinical outcomes of the regimen in those patients. We finally evaluated 53 patients with symptomatic NGU and 5 patients with asymptomatic NGU. As a result of microbiological examinations, 19 of the symptomatic patients were diagnosed as having non-gonococcal chlamydial urethritis (NGCU); 13 had non-gonococcal non-chlamydial urethritis (NGNCU), and 21 had urethritis without any microbial detection. Five of the asymptomatic patients were diagnosed as having NGCU. Microbiological cure was achieved in 91% of the 32 patients with symptomatic NGU and in 80% of the 5 patients with asymptomatic NGCU. Clinical cure was obtained in 92% of the 53 patients with symptomatic NGU. The microbiological eradication rate for Chlamydia trachomatis was 92% in 24 patients. As for other organisms, the microbiological eradication rate for Mycoplasma genitalium was 60% in 5 patients and that for Ureaplasma urealyticum was 100% in 10. The microbiological and clinical efficacy of oral LVFX 500 mg once daily for 7 days for the patients with NGU was the same for the azithromycin (AZM) 1,000 mg single dose that we previously reported. The eradication rates of C. trachomatis and U. urealyticum in the treatment regimen with LVFX 500 mg were high enough in the clinical setting; however, for M. genitalium, the rate was relatively inferior to that with AZM.

Management for males whose female partners are diagnosed with genital chlamydial infection.

The purpose of this study was to investigate the infection rate of asymptomatic men whose female sexual partners were diagnosed as having genital chlamydial infection and discuss the management for them. The subjects were asymptomatic men whose female sexual partners were diagnosed with genital chlamydial infection at other obstetric and gynecological clinics. Microscopic findings of urinary sediment and the results of a nucleic acid amplification test of the first-voided urine specimen were retrospectively examined in those men who visited our clinics. A total of 267 men were included and analyzed. The infection rate for urinary Chlamydia trachomatis in asymptomatic men was 36.3% (97 of 267). In the analysis of urinary sediment, 35 of the 267 (13.1%) had pyuria and 82.9% (29 of 35) in the men with pyuria were positive for urinary C. trachomatis in. Even in men without pyuria, the urinary C. trachomatis-positive rate was 29.3% (68 of 232). When such men have pyuria in the clinic, prompt treatment is the appropriate approach. If the men are without pyuria, testing for urinary C. trachomatis should be performed. Prompt treatment before doing any clinical evaluation can be an option in couples with trouble.