Silver-Catalyzed para-Selective Sulfenyl Group Transfer Reactions of N-Sulfenylanilides.

Silver-catalyzed reactions of N-sulfenylanilides afforded the corresponding p-sulfenylanilides in good to high yields with good para selectivity. The transformation has a high compatibility of functional groups, such as ester, bromo, and iodo groups. Mechanistic studies indicate that the rearrangement reaction proceeds through intermolecular transfer of the sulfenyl group.

Peripheral Parenteral Nutrition Solutions and Bed Bath Towels as Risk Factors for Nosocomial Peripheral Venous Catheter-related Bloodstream Infection by Bacillus cereus.

In Japan, China, and Singapore, several studies have reported increased incidences of peripheral venous catheter-related bloodstream infection by Bacillus cereus during the summer. Therefore, we hypothesized that bed bathing with a B. cereus-contaminated "clean" towels increases B. cereus contact with the catheter and increases the odds of contaminating the peripheral parenteral nutrition (PPN). We found that 1) professionally laundered "clean" towels used in hospitals have B. cereus (3.3×104 colony forming units (CFUs) / 25cm2), 2) B. cereus is transferable onto the forearms of volunteers by wiping with the towels (n=9), and 3) B. cereus remain detectable (80∼660 CFUs /50cm2) on the forearms of volunteers even with subsequent efforts of disinfection using alcohol wipes. We further confirmed that B. cereus grow robustly (102 CFUs /mL to more than 106 CFUs /mL) within 24hours at 30°C in PPN. Altogether we find that bed bathing with a towel contaminated with B. cereus leads to spore attachments to the skin, and that B. cereus can proliferate at an accelerated rate at 30°C compared to 20°C in PPN. We therefore highly recommend ensuring the use of sterile bed bath towels prior to PPN administration with catheter in patients requiring bed bathing.

Comparison of methylprednisolone pulse vs conventional dexamethasone for adult cases of COVID-19 requiring oxygen; a Japanese retrospective cohort study.

BACKGROUND: Although dexamethasone is an effective treatment in cases of coronavirus disease 2019 (COVID-19) requiring oxygen, the efficacy of methylprednisolone pulse is unclear. We compared the characteristics and outcomes of methylprednisolone pulse to those of dexamethasone. METHODS: We conducted a retrospective cohort study on adult COVID-19 cases requiring oxygen and no invasive mechanical ventilation treated with methylprednisolone pulse (1 g/day for 3 days) or dexamethasone (6 mg/day orally or 6.6 mg/day intravenously for ≥5 days). The primary outcome was intensive care unit (ICU) admission. The secondary outcomes were hospital mortality, length of hospital stay (LoS), duration of oxygen requirement, and requirement for hospital transfer, vasopressor(s), intubation, extracorporeal membrane oxygenation (ECMO), and continuous renal replacement therapy (CRRT). RESULTS: Twenty two cases of methylprednisolone pulse and 77 cases of dexamethasone were included. Mask ventilation was more common in the methylprednisolone pulse group (P < 0.001). The proportion of ICU admissions was similar between both groups (P = 0.635). The secondary outcomes of hospital mortality and the requirement for hospital transfer, vasopressor(s), intubation, and CRRT were similar between groups. No cases received ECMO. Median LoS (P = 0.006) and duration of oxygen requirement (P = 0.004) were longer in the methylprednisolone pulse group. CONCLUSIONS: The proportion of ICU admissions was similar between the methylprednisolone pulse and the dexamethasone group. However, more cases in the methylprednisolone pulse group required mask ventilation than in the dexamethasone group, suggesting that some cases benefited from methylprednisolone pulse.

Synthesis of meta-Aminophenol Derivatives via Cu-Catalyzed [1,3]-Rearrangement-Oxa-Michael Addition Cascade Reactions.

Cu-catalyzed reactions of N-alkoxy-2-methylanilines and alcohols in the presence of catalytic amounts of IPrCuBr and AgSbF6 afforded the corresponding meta-aminophenol derivatives in good to high yields. These reactions proceed via a [1,3]-rearrangement, in which the alkoxy group migrates from the nitrogen atom to the methyl-substituted ortho position, followed by an oxa-Michael reaction of the resulting ortho-quinol imine intermediate.

Kidney vascular congestion exacerbates acute kidney injury in mice.

Heart failure is frequently accompanied by kidney failure and co-incidence of these organ failures worsens the mortality in patients with heart failure. Recent clinical observations revealed that increased kidney venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in patients with heart failure. However, the underlying pathophysiology is unknown. Here, we found that decreased blood flow velocity in peritubular capillaries by kidney congestion and upregulation of endothelial nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral kidney congestion by constriction of the inferior vena cava between kidney veins. Intravital imaging highlighted the notable dilatation of peritubular capillaries and decreased kidney blood flow velocity in the congestive kidney. Damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes within peritubular capillaries was noted at the acute phase after injury. Similar results were obtained in vitro, in which polymorphonuclear leukocytes adhesion on activated endothelial cells was decreased in flow velocity-dependent manner but cancelled by inhibition of NF-κB signaling. Pharmacological inhibition of NF-κB for the mice subjected by both kidney congestion and ischemia reperfusion injury ameliorated the accumulation of polymorphonuclear leukocytes and subsequent exacerbation of kidney injury. Thus, our study demonstrates the importance of decreased blood flow velocity accompanying activated NF-κB signaling in aggravation of kidney injury. Hence, inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased kidney venous pressure.

Persistence of Mental Health Deterioration Among People Living Alone During the COVID-19 Pandemic: A Periodically-repeated Longitudinal Study.

BACKGROUND: This longitudinal study aimed to investigate how psychological distress levels changed from early to middle phases of the new coronavirus (COVID-19) pandemic depending on the living arrangements of individuals. METHODS: An internet-based, longitudinal survey of 2,400 Japanese people was conducted every 5-6 weeks between February 2020 and January 2021. The presence of severe psychological distress (SPD) was measured using the Kessler's psychological distress scale. Living arrangements were classified into two groups (ie, living alone or living with others). Mixed-effects logistic regression analysis was performed to assess whether changes in SPD status were different depending on living arrangements. RESULTS: Of 2,400 respondents, 446 (18.5%) lived alone. Although the proportion of SPD in both individuals living alone and those living with others increased to the same extent in the early phase of the pandemic, the distress levels decreased after the early phase of the pandemic in the group living with others, compared with the group living alone, for which SPD remained high. The odds ratio (OR) of developing SPD in interaction term with survey phases tended to be higher among those who lived alone than those who lived with others in Phase 6 (OR 1.89; 95% confidence interval [CI], 0.99-3.64) and Phase 7 (OR 1.88; 95% CI, 0.97-3.63). CONCLUSION: During the COVID-19 pandemic, those living alone are persistently at a higher risk of SPD compared to those living with others. Effective countermeasures targeting those living alone, such as enhancing online communication or providing psychological therapies, are essential.

Case of sexually transmitted recurrent pharyngotonsillitis caused by group A streptococcus.

We report a five-time recurrent pharyngotonsillitis caused by group A streptococcus (GAS) after sexual contacts and had no recurrence after concurrent therapy to both partners. Although Streptococcus pyogenes (GAS) is a Gram-positive streptococcus capable of causing a recurrent pharyngotonsillitis, the recurrent GAS pharyngotonsillitis as STI has not been published.A 30-year-old man had a high fever and sore throat. He had a repeated pharyngotonsillitis caused by GAS in spite of the sufficient antimicrobial therapy after having sex with his partner, including oral penile and oral vaginal sex. In contrast, a hug and kiss alone did not precede his episodes of pharyngotonsillitis. His partner had GAS carriage on her pharynx. He had no recurrence after concurrent therapy to both partners. The recurrent GAS pharyngotonsillitis as STI has not been published. In a patient with recurrent pharyngotonsillitis caused by GAS, the sexual history and pharyngeal carrier status of the partner should be checked.

Hypertrophic pachymeningitis caused by Schizophyllum sp.: a novel case report.

BACKGROUND: The pathogenic fungus Schizophyllum sp. can cause allergic fungal rhinosinusitis and allergic bronchopulmonary mycosis in humans. Sinus and lung infections due to Schizophyllum sp. have been reported globally; however, no case of hypertrophic pachymeningitis due to this pathogen has been reported yet. Herein, we describe for the first time, a case of hypertrophic pachymeningitis due to Schizophyllum sp. CASE PRESENTATION: A 69-year-old woman visited the hospital with chief complaints of headache, right trigeminal neuralgia (third branch), ataxic gait, and deafness in the right ear. Magnetic resonance imaging revealed a tumor in the right sphenoidal sinus and thickening of the dura mater surrounding the right porus acusticus internus. Endoscopic sinus surgery and neuroendoscopic biopsy were performed to remove sinus lesions and intracranial lesions, respectively. Both pathological specimens showed findings indicative of filamentous fungi on Grocott's staining. DNA sequencing with the sinus specimen revealed Schizophyllum sp. as the causative pathogen, consistent with the diagnosis of fungal sinusitis and hypertrophic pachymeningitis. Intravenous liposomal amphotericin B was started, but owing to lack of improvement, the treatment was switched to intravenous voriconazole. We observed improvements in both radiological findings and symptoms. However, the symptoms exacerbated again when the trough level of voriconazole decreased. Upon increasing the voriconazole dose, a higher trough level was obtained and the symptoms improved. CONCLUSION: Our study suggests that when symptoms of central nervous system infection due to Schizophyllum sp. do not improve with liposomal amphotericin B, voriconazole can be administered at high trough levels to improve the symptoms.

Case report of restless anal syndrome as restless legs syndrome variant after COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a broad spectrum from respiratory and nasopharyngeal symptoms, cerebrovascular diseases, impaired consciousness, and skeletal muscle injury. Emerging evidence has indicated the neural spread of this novel coronavirus. Restless legs syndrome (RLS) is a common neurological, sensorimotor disorder, but highly under diagnosis disorder. Restless anal syndrome as restless legs syndrome variant associated with COVID-19 has been previously not published. We report a case presenting with restless anal syndrome following COVID-19. CASE PRESENTATION: Although a 77-year-old male with COVID-19 improved to normal respiratory function 21 days after admission and treatment of favipiravir 200 mg per day for 14 days and dexamethasone 6.6 mg per day for 5 days, the insomnia and anxiety symptoms remained. Several weeks after discharge, he gradually began to experience restless, deep anal discomfort, approximately 10 cm from the perineal region. The following features were observed in the anal region; urge to move is essential, with worsening with rest, improvement with exercise, and worsening at evening. Colonoscopy revealed internal haemorrhoids without other rectal lesions. Neurological findings including deep tendon reflex, perineum loss of sensory and spinal cord injury, revealed no abnormalities. Diabetes militias, kidney dysfunction and iron deficiency status were not confirmed. Family history of RLS and periodic limb movements were not observed. Clonazepam at 1.5 mg per day resulted in the alleviation restless anal discomfort. CONCLUSIONS: We reported a case presenting with restless anal syndrome following affection of COVID-19 as restless legs syndrome variant. This case fulfilled 4 essential features of RLS, urge to move, worsening with rest, improvement with exercise, and worsening at evening. To date, no case of restless anal syndrome associated with COVID-19 has been previously published. This case report may reflect the associative impacts of COVID-19 on the neuropsychiatric state. The long-term outcomes of neuropsychiatric conditions should continue to be monitored.

The seasonality, steroid use, and lower ratio of neutrophil to lymphocyte associated with bacteremia of Listeria monocytogenes in Japan from 2010 to 2019: a case-control study.

BACKGROUND: Despite having a high mortality rate, Asian studies about the characteristics of adult listeriosis are limited. We investigated the incidence of listeriosis per admissions, associated factors, and rate of mortality in listeriosis, compared with non-listeriosis. METHODS: We recorded the incidence of listeriosis per 10,000 admissions and conducted a case-control study from January 1, 2010, to December 31, 2019, at Tokyo Medical University Hospital (TMUH) in Japan. Cases were defined as adult with listeriosis that was bacteremia due to L. monocytogenes. Controls, defined as adult with non-listeriosis bacteremia due to other pathogens, were matched by age and clinical department to cases. We analyzed differences in seasonality, including warm season (defined as the period from May to October), medication including steroids, laboratory findings, and mortality. The odds ratio and p value between the cases group and control group were calculated using a chi-square test and Fisher's exact test. RESULTS: The incidence of listeriosis per 10,000 admissions to TMUH was 0.51. Eleven patients, excluding one neonate, were included in the case group. Twenty-six patients, excluding one patient because of contamination and one patient because of insufficient medical record, were included in the control group. Listeriosis onset was associated with the warm season (90.9% vs. 53.8%; p = 0.033), steroid use (54.5% vs. 19.2%; p = 0.042), and a lower ratio of neutrophils to lymphocytes (9.46 vs. 18.44; p = 0.015). The 30-day mortality rate of listeriosis was similar to non-listeriosis (18.3% vs. 19.2%; p = 0.619). CONCLUSION: The incidence of listeriosis per admissions in this study was similar to that in other Asian countries. Factors associated with listeriosis were the warm season, steroid use, and a lower ratio of neutrophils to lymphocytes. Additionally, the 30-day mortality rate was similarly high in both the listeriosis and non-listeriosis groups.

Refractory pharyngeal ulceration due to cytomegalovirus in a patient with HIV infection: a case report and literature review.

BACKGROUND: Cytomegalovirus (CMV) is an important pathogen among immunocompromised hosts. Typically, CMV in human immunodeficiency virus (HIV) infection causes diseases of the retina, digestive tract, lungs and liver, but there are few cases of CMV infection of the pharynx and larynx. CASE PRESENTATION: A 57-year-old man with HIV infection was admitted because of pharyngeal pain. Before and after admission, pharyngeal biopsies guided by laryngeal endoscopy were performed four times, but pathological examination showed nonspecific inflammation, and the cause of pharyngeal ulceration was unclear. Additionally, the ulceration deteriorated after initiation of retroviral therapy. Laryngomicrosurgery was conducted under general anesthesia to remove tissue, and pathological diagnosis confirmed CMV infection. Pathological features included enlargement of the cytoplasm and nucleus in infected cells, and intranuclear bodies called owl's eye inclusions. Ganciclovir dramatically improved the symptoms and laryngoscopic findings. CONCLUSIONS: This case was diagnosed as pharyngitis and pharyngeal ulceration caused by CMV infection, related to immune reconstitution inflammatory syndrome. In previous reports of CMV-induced pharyngeal or laryngeal ulceration in HIV infection, we found six cases similar to our present case. All cases were diagnosed by biopsy. The present case indicates the importance of biopsy for definitive diagnosis. CMV infection should be considered as a differential diagnosis of pharyngeal ulceration in patients with HIV infection.

Consecutive O-S/N-S Bond Cleavage in Gold-Catalyzed Rearrangement Reactions of Alkynyl N-Sulfinylimines.

Gold-catalyzed reactions of alkynyl N-sulfinylimines were used to produce the corresponding 2H-azirines possessing sulfenyl and acyl groups at the 3-position of the azirine ring in good to excellent yields. These reactions involved internal transfer of the sulfinyl oxygen atom to form a thiooxime intermediate tethered to an α-oxo gold carbene moiety. Subsequent insertion of the carbene into the N-S bond resulted in ring construction.

Imipenem plus Fosfomycin as Salvage Therapy for Vertebral Osteomyelitis.

We applied combination antibiotic therapy to treat vertebral osteomyelitis and a psoas abscess caused by glycopeptide-intermediate (MIC, 2 µg/ml) and daptomycin-nonsusceptible (>2 µg/ml) methicillin-resistant Staphylococcus aureus The Etest synergy test showed the largest synergistic effects for imipenem/cilastatin and fosfomycin. Whole-gene sequencing showed amino acid changes in SA0802, SA1193 (mprF), and SA1531 (ald). Four weeks of combination treatment using imipenem/cilastatin (1.5 g per day) and fosfomycin (4.0 g per day) resulted in clinical improvement.

Exo-Cyclization: Intermolecular Methylene Transfer Sequence in Au-Catalyzed Reactions of O-Homopropargylic Oximes.

The Au-catalyzed reactions of O-homopropaylic oximes afforded the 3-alkenylated isoxazolines in good to high yields. The mechanistic studies suggest that the reaction proceeds through an exo-cyclization followed by intermolecular methylene group transfer. In addition, oligomeric species of the starting material were observed in the reaction mixture by mass spectra, supporting our proposed mechanism, which proceeds through a repeated intermolecular C-C bond forming process.

Disseminated Bacillus Calmette-Guérin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review.

BACKGROUND: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. CASE PRESENTATION: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. CONCLUSIONS: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.

Changes in Psychological Distress During the COVID-19 Pandemic in Japan: A Longitudinal Study.

BACKGROUND: This longitudinal study aimed to examine the changes in psychological distress of the general public from the early to community-transmission phases of the COVID-19 pandemic and to investigate the factors related to these changes. METHODS: An internet-based survey of 2,400 Japanese people was conducted in two phases: early phase (baseline survey: February 25-27, 2020) and community-transmission phase (follow-up survey: April 1-6, 2020). The presence of severe psychological distress (SPD) was measured using the Kessler's Six-scale Psychological Distress Scale. The difference of SPD percentages between the two phases was examined. Mixed-effects ordinal logistic regression analysis was performed to assess the factors associated with the change of SPD status between the two phases. RESULTS: Surveys for both phases had 2,078 valid respondents (49.3% men; average age, 50.3 years). In the two surveys, individuals with SPD were 9.3% and 11.3%, respectively, demonstrating a significant increase between the two phases (P = 0.005). Significantly higher likelihood to develop SPD were observed among those in lower (ie, 18,600-37,200 United States dollars [USD], odds ratio [OR] 1.95; 95% confidence interval [CI], 1.10-3.46) and the lowest income category (ie, <18,600 USD, OR 2.12; 95% CI, 1.16-3.86). Furthermore, those with respiratory diseases were more likely to develop SPD (OR 2.56; 95% CI, 1.51-4.34). CONCLUSIONS: From the early to community-transmission phases of COVID-19, psychological distress increased among the Japanese. Recommendations include implementing mental health measures together with protective measures against COVID-19 infection, prioritizing low-income people and those with underlying diseases.

Copper-Catalyzed Domino [1,3]/[1,2] Rearrangement for the Efficient Synthesis of Multisubstituted ortho-Anisidines.

Multisubstituted ortho-anisidines were efficiently synthesized via cationic N-heterocyclic carbene-Cu-catalyzed domino rearrangement of N-methoxyanilines that possess an electron-donating functional group, such as an alkyl or an aryl group, at the ortho position. The reaction proceeded first through a [1,3]-rearrangement of the methoxy group to the ortho position bound to the electron-donating substituent, followed by a semipinacol type [1,2]-rearrangement of the electron-donating group from the ortho to the meta position. Mechanistic studies suggest that both rearrangement reactions are promoted by a cationic Cu catalyst.

Bacille Calmette-Guérin (BCG) spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy: a case report and literature review.

BACKGROUND: Although intravesical bacille Calmette-Guérin (BCG) therapy is accepted as an effective treatment for bladder cancer, serious complications may occur in rare cases. To date, only 4 cases have been reported in which the patient developed a combination of mycotic aortic aneurysm and BCG spondylitis. Accurate diagnosis of BCG spondylitis is important because it is an iatrogenic disease, and its treatment is different from usual tuberculous spondylitis. However, distinguishing BCG spondylitis from usual tuberculous spondylitis is very difficult and takes a long time. In this study, we were able to suspect BCG spondylitis at an early stage from the result of the interferon-gamma release assay (IGRA). CASE PRESENTATION: We encountered a case of BCG spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy in a 76-year-old man. We performed a 2-stage operation to obtain spine stabilization and replace the aneurysm with a synthetic graft. We started multidrug therapy with antituberculosis medication, excluding pyrazinamide, because the patient's history of BCG therapy, negative IGRA, and positive of tuberculosis-polymerase chain reaction (Tb-PCR) suggested that the pathogenic bacteria of the spondylitis was BCG. Eventually the bacterial strain was identified as BCG by PCR-based genomic deletion analysis. CONCLUSIONS: BCG infection should be considered in patients who have been treated with BCG therapy, even if the treatment was performed several months to several years previously. In the case of a patient with a history of BCG therapy, a positive Tb-PCR result and negative IGRA result probably suggest BCG infections, if the possibility of false-negative IGRA result can be excluded.

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines.

A cationic cobalt catalyst efficiently promoted the reaction of N-alkoxycarbonyloxyanilines at 30 °C, affording the corresponding ortho-aminophenols in good to high yields. As reported previously, our mechanistic studies including oxygen-18 labelling experiments indicate that the rearrangement of the alkoxycarbonyloxy group proceeds in [1,3]-manner. In this article, we discuss the overall picture of the cobalt-catalysed [1,3]-rearrangement reaction including details of the reaction conditions and substrate scope.

Rapid Access to Nitrogenous Heterobicycles via RhIII -Catalyzed Isomerization from Alkynes to Allenes.

We show that N-alkynylnitrones are efficiently converted to nitrogenous heterobicyclic compounds with a nitrogen atom at the bridgehead position by using a RhIII -catalyst. Our mechanistic studies suggest that the reaction proceeds via an allene intermediate, which is generated in situ through RhIII -catalyzed isomerization of the alkyne group.