Epidemiology of post-COVID conditions beyond 1 year: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the epidemiology of post-COVID conditions beyond 12 months and identify factors associated with the persistence of each condition. STUDY DESIGN: This was a cross-sectional questionnaire-based survey. METHODS: We conducted the survey among patients who had recovered from COVID-19 and visited our institute between February 2020 and November 2021. Demographic and clinical data and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the persistence of post-COVID conditions using multivariable linear regression analyses. RESULTS: Of 1148 surveyed patients, 502 completed the survey (response rate, 43.7%). Of these, 393 patients (86.4%) had mild disease in the acute phase. The proportion of participants with at least one symptom at 6, 12, 18, and 24 months after symptom onset or COVID-19 diagnosis was 32.3% (124/384), 30.5% (71/233), 25.8% (24/93), and 33.3% (2/6), respectively. The observed associations were as follows: fatigue persistence with moderate or severe COVID-19 (ß = 0.53, 95% confidence interval [CI] = 0.06-0.99); shortness of breath with moderate or severe COVID-19 (ß = 1.39, 95% CI = 0.91-1.87); cough with moderate or severe COVID-19 (ß = 0.84, 95% CI = 0.40-1.29); dysosmia with being female (ß = -0.57, 95% CI = -0.97 to -0.18) and absence of underlying medical conditions (ß = -0.43, 95% CI = -0.82 to -0.05); hair loss with being female (ß = -0.61, 95% CI = -1.00 to -0.22), absence of underlying medical conditions (ß = -0.42, 95% CI = -0.80 to 0.04), and moderate or severe COVID-19 (ß = 0.97, 95% CI = 0.41-1.54); depressed mood with younger age (ß = -0.02, 95% CI = -0.04 to -0.004); and loss of concentration with being female (ß = -0.51, 95% CI = -0.94 to -0.09). CONCLUSIONS: More than one-fourth of patients after recovery from COVID-19, most of whom had had mild disease in the acute phase, had at least one symptom at 6, 12, 18, and 24 months after onset of COVID-19, indicating that not a few patients with COVID-19 suffer from long-term residual symptoms, even in mild cases.

Post COVID-19 condition of the Omicron variant of SARS-CoV-2.

OBJECTIVES: To investigate the prevalence of post coronavirus disease (COVID-19) condition of the Omicron variant in comparison to other strains. STUDY DESIGN: A single-center cross-sectional study. METHODS: Patients who recovered from Omicron COVID-19 infection (Omicron group) were interviewed via telephone, and patients infected with other strains (control group) were surveyed via a self-reporting questionnaire. Data on patients' characteristics, information regarding the acute-phase COVID-19, as well as presence and duration of COVID-19-related symptoms were obtained. Post COVID-19 condition in this study was defined as a symptom that lasted for at least 2 months, within 3 months of COVID-19 onset. We investigated and compared the prevalence of post COVID-19 condition in both groups after performing propensity score matching. RESULTS: We conducted interviews for 53 out of 128 patients with Omicron and obtained 502 responses in the control group. After matching cases with controls, 18 patients from both groups had improved covariate balance of the factors: older adult, female sex, obesity, and vaccination status. There were no significant differences in the prevalence of each post COVID-19 condition between the two groups. The number of patients with at least one post COVID-19 condition in the Omicron and control groups were 1 (5.6%) and 10 (55.6%) (p = 0.003), respectively. CONCLUSIONS: The prevalence of post Omicron COVID-19 conditions was less than that of the other strains. Further research with a larger sample size is needed to investigate the precise epidemiology of post COVID-19 condition of Omicron, and its impact on health-related quality of life and social productivity.

Nanosecond Random Telegraph Noise in In-Plane Magnetic Tunnel Junctions.

We study the timescale of random telegraph noise (RTN) of nanomagnets in stochastic magnetic tunnel junctions (MTJs). From analytical and numerical calculations based on the Landau-Lifshitz-Gilbert and the Fokker-Planck equations, we reveal mechanisms governing the relaxation time of perpendicular easy-axis MTJs (p-MTJs) and in-plane easy-axis MTJs (i-MTJs), showing that i-MTJs can be made to have faster RTN. Superparamagnetic i-MTJs with small in-plane anisotropy and sizable perpendicular effective anisotropy show relaxation times down to 8 ns at negligible bias current, which is more than 5 orders of magnitude shorter than that of typical stochastic p-MTJs and about 100 times faster than the shortest time of i-MTJs reported so far. The findings give a new insight and foundation in developing stochastic MTJs for high-performance probabilistic computers.

Nightlife clusters of coronavirus disease in Tokyo between March and April 2020.

We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.

Adherence to personal protective equipment use among nurses in Japanese tertiary care hospitals: what determines variability?

BACKGROUND: Though nurses have frequent contact with patients, their personal protective equipment (PPE) compliance rate is low, which poses a significant challenge in infection control. AIM: To investigate the relative influence of specific factors on PPE compliance. METHODS: A sequential two-stage mixed-methods design was applied. In a qualitative study, semi-structured interviews were conducted from May to July 2018. In a quantitative study, a nationwide, cross-sectional survey was conducted from January to March 2019, in which a questionnaire was mailed to 735 nurses in 28 tertiary care hospitals in Japan. FINDINGS: In the quantitative study, 435 (59.2%) analysable responses were obtained. In the linear regression analysis, the lack of the knowledge that 'standard precaution was the fundamental infection countermeasure applied when patients had signs of infections, and these countermeasures could be terminated if there was no infection found' was significantly associated with decreased PPE adherence, whereas an antimicrobial-resistant bacteria outbreak or a ward shutdown due to an outbreak and the belief 'I must never be the cause of spreading infection' were significantly associated with increased PPE adherence. The ß of standard coefficients and t-values of the items were -0.344, -7.784, 0.090, 2.089, 0.088, 2.018, respectively. CONCLUSION: This survey systematically identified nursing-associated factors that contribute to PPE compliance. As a practical approach to ensure positive outcomes, we suggest educating nurses by providing adequate knowledge on appropriate PPE use and sharing outbreak or ward shutdown experiences.

Adherence to contact precautions by different types of healthcare workers through video monitoring in a tertiary hospital.

BACKGROUND: Contact precautions are required to prevent transmission of multi-drug-resistant organisms; however, reports on adherence rates vary. This study used video monitoring to evaluate adherence to the use of personal protective equipment (PPE) by different types of healthcare workers. METHODS: This observational study was conducted in a 781-bed tertiary hospital from July 2016 to March 2017. Cameras were installed in areas where staff don PPE. Infection control teams observed the videos and assessed adherence rates. RESULTS: In total, 1097 opportunities for donning PPE were observed. Most staff observed were nurses and nursing assistants (Ns/Nsas) (880/1097, 80.2%). Overall, the adherence rate to appropriate PPE use was 34.0%. The adherence rate among Ns/Nsas was lower (239/858, 27.9%) compared with infectious disease doctors (18/18, 100%) and cleaning staff (42/49, 85.7%). The adherence rate for PPE use for Clostridium difficile infection (CDI) with toxin detection was significantly higher than that for CDI without toxin detection and multi-drug-resistant organisms (P<0.001 for both). The adherence rate for patients with an independent functional status was higher than that for patients with a dependent functional status (P=0.018). The adherence rate was lower in the intensive care unit (ICU) than in non-ICU wards (27.6% vs 36.5%; P=0.006). CONCLUSION: Video monitoring is a useful tool for monitoring adherence to PPE use, facilitating observation of more PPE opportunities than direct observation. Adherence to contact precautions varied by occupation; however, overall adherence was insufficient. The lower adherence rate in nurses might be due to more frequent care visits.

Spatial variations of 226Ra, 228Ra, 134Cs, and 137Cs concentrations in western and southern waters off the Korean Peninsula in July 2014.

We examined the spatial distributions of 226Ra, 228Ra, 134Cs, and 137Cs concentrations (activities) in seawater off the western and southern Korean Peninsula in July 2014. Radium-228 (and 226Ra) concentrations in water samples varied widely from 5 to 14 mBq/L (2-4 mBq/L), showing a negative correlation with salinity, particularly at the surface off the western Korean Peninsula. This indicates that the seawaters in this area are fundamentally comprised of 228Ra-poor and high-saline Kuroshio Current water and 228Ra-rich and low-saline water (e.g., continental shelf water), with various mixing ratios. Although Fukushima Dai-ichi Nuclear Power Plant (FDNPP)-derived 134Cs was below the detection limit (<0.08 mBq/L) in waters off the western Korean Peninsula, low level 134Cs (0.1-0.2 mBq/L) was detected in waters off the southern Korean Peninsula accompanied by higher 137Cs concentrations (1.6-1.9 mBq/L) relative to that off the western Korean Peninsula. Combined with the lower radium concentrations, the detection of 134Cs is explained by mixing of FDNPP-derived radiocesium-contaminated Kuroshio Current water.

Impact of prompt intervention in response to positive blood culture results during weekends by collaboration between infectious disease specialists and microbiology laboratory staff.

The purpose of this investigation was to elucidate the impact of prompt intervention for patients whose blood culture results became positive during weekends, as this is not standard care in some countries. A retrospective cohort study was conducted in a tertiary referral hospital. From June 2015, results of positive blood cultures became available during weekends. If infectious disease specialists identified cases of bacteremia on suboptimal antimicrobial coverage, they contacted the primary team for modification of antibiotic treatment. We reviewed patients whose blood culture results became positive during weekends, comparing the pre-intervention (September 2014 to May 2015) and post-intervention (June 2015 to February 2016) periods. In total, 1081 (post-intervention 568 [52.5%]) bacteremia episodes were included (median patient age [interquartile range, IQR]: 72 [60-82] years; men: 625 [57.8%]). During the post-intervention period, 187 (32.9%) bacteremia episodes were detected during weekends. Infectious disease specialists evaluated the positive blood culture results 1, 2, and ≥3 days prior in 77 (13.6%), 88 (15.5%), and 22 (3.9%) cases, respectively. Although the 7- and 30-day mortality did not significantly improve after the intervention, the length of hospital stay (LOS) in the hospital-acquired bacteremia group was significantly reduced during the post-intervention period after controlling for confounders (post- vs. pre-intervention: median days [IQR]: 37 [19-63] vs. 46.5 [24.8-86.3], p = 0.030). Blood culture results became positive during weekends in one-third of bacteremia cases. The LOS was shortened after the intervention in the hospital-acquired bacteremia group. This could be an important antimicrobial stewardship target.

Evaluation of genetic factors involved in nocturnal electromyographic activity of masticatory muscles in twins.

OBJECTIVES: The objectives of this study were to assess sleep bruxism events by directly recording electromyographic activity during sleep and to reveal the relative importance of genetic and environmental factors involved in sleep bruxism in twins. MATERIAL AND METHODS: The subjects consisted of 108 twins (mean age 22.2 ± 6.4 years). Electromyographic activity of temporalis muscles during sleep was evaluated using a portable automatic sleep bruxism analyzer (Grindcare 3.0, Medotech A/S), and recordings were carried out for at least three consecutive nights. Quantitative genetic statistics based on structural equation modeling was utilized to estimate variance components. RESULTS: Monozygotic twin-pair correlation for the number of nocturnal electromyographic activities recorded in this study (r = 0.463, P = 0.009) was higher than dizygotic twin-pair correlation (r = 0.103, P = 0.725). The proportion of total phenotypic variance in the liability of sleep bruxism to attribute to genetic influences, related to the electromyographic activities, was 48 % (95 % CI 17-95 %) and to unique environmental influences was 52 % (95 % CI 28-82 %). CONCLUSIONS: Additive genetic effects may be a contributing factor to the occurrence of nocturnal EMG activity associated with sleep bruxism. CLINICAL RELEVANCE: A greater understanding of the contribution of genetic factors could have beneficial uses, including enhanced accuracy of sleep bruxism diagnosis, management of sleep bruxism, and enhanced estimation of the prognosis for patients suffering from sleep bruxism. In addition, it could be also important to adequately evaluate the environmental factors in patients with sleep bruxism.

Loss of a chromosomal region with synteny to human 13q14 occurs in mouse chronic lymphocytic leukemia that originates from early-generated B-1 B cells.

A common feature of B-cell chronic lymphocytic leukemia (CLL) is chromosomal loss of 13q14, containing the miR15a/16-1 locus controlling B-cell proliferation. However, CLL etiology remains unclear. CLL is an adult leukemia with an incidence that increases with advancing age. A unique feature of CLL is biased B-cell antigen receptor (BCR) usage, autoreactivity with polyreactivity and CD5 expression, all suggest a role for the BCR in driving CLL pathogenesis. Among human CLLs, BCRs autoreactive with non-muscle myosin IIA (AMyIIA) are recurrent. Here we identify an unmutated AMyIIA BCR in mouse, with distinctive CDR3 segments capable of promoting leukemogenesis. B cells with this AMyIIA BCR are generated by BCR-dependent signaling during B-1 fetal/neonatal development with CD5 induction, but not in adults. These early-generated AMyIIA B-1 B cells self-renew, increase during aging and can progress to become monoclonal B-cell lymphocytosis, followed by aggressive CLL in aged mice, often with the loss of a chromosomal region containing the miR15a/16-1 locus of varying length, as in human CLL. Thus, the ability to generate this defined autoreactive BCR by B-1 B cells is a key predisposing step in mice, promoting progression to chronic leukemia.

Influence of genetic and environmental factors on oral diseases and function in aged twins.

This study was conducted to quantify the genetic and environmental contributions to oral disease and function in twins. Participants were middle-aged and old twins, 116 monozygotic and 16 dizygotic pairs whose mean age was 66·1 ± 10·3 (SD) years. Number of teeth, percentage of decayed, filled and missing teeth and periodontal status were recorded as indicators of oral disease. The widths of upper and lower dental arch served as indicators of morphological figures. Furthermore, stimulated salivary flow rate, occlusal force and masticatory performance were measured as indicators of oral function. Univariate genetic analysis with monozygotic and dizygotic twin pairs was conducted to detect the fittest structural equation model of each outcome. Both number of teeth and periodontal status fitted the model composed of common environmental factor and unique environmental factor. Decayed, filled and missing teeth, morphological figures and measurements of oral function fitted the model composed of additive genetic factor and unique environmental factor. The model fitting of each measurement suggested that periodontal disease was mainly affected by environmental factors, while morphological figures and oral functions were influenced by both genetic and environmental factors.

Treatment results for Stage Ib cervical cancer after stage subdivision by MRI evaluation.

PURPOSE OF INVESTIGATION: The authors analyzed treatment results for cervical cancer after subdividing Stage Ib into Stages Ib1 and Ib2 according to magnetic resonance imaging (MRI) information. MATERIALS AND METHODS: The subjects comprised 40 cases of Stage Ib cervical cancer treated by definitive radiotherapy in Kitasato University hospital and Tokyo University hospital from January 2000 to December 2008. The patients' ages ranged from 28 to 85 years (median: 68 years). The maximum tumor diameter measured with MRI ranged from undetectable to 60 mm (median: 25 mm). The authors classified tumors with the greatest dimension less than 40 mm as Stage Ib1 (29 cases) and those with the greatest dimension more than 40 mm as Ib2 (11 cases). All cases were treated with a combination of external beam irradiation and high-dose-rate intra-cavitary brachytherapy. Chemotherapy was combined with radiotherapy in 11 cases. RESULTS: The follow-up time was from four to 109 months (median: 53 months). At the time of last observation, 37 cases survived, local recurrence was seen in none, and two cases showed distant metastasis. The two- and five-year overall survival rates of all cases were 97.5% and 89.5%, respectively. When a stage was subdivided and examined, the five-year overall survival rate of Stage Ib1 was 100% and that of Stage Ib2 was 50.5% (p = 0.001). CONCLUSION: The authors suggest that the subdivision of stages using image information reflects the prognosis of Stage Ib cervical cancer.

Mechanisms of neurovascular dysfunction in acute ischemic brain.

The neurovascular unit is now well accepted as a conceptual framework for investigating the mechanisms of ischemic stroke. From a molecular and cellular perspective, three broad mechanisms may underlie stroke pathophysiology--excitotoxicity, oxidative stress and inflammation. To date, however, most investigations of these basic mechanisms have focused on neuronal responses. In this mini-review, we ask whether these mechanisms of excitotoxicity, oxidative stress and inflammation can also be examined in terms of non-neuronal interactions in the neurovascular unit, including the release of extracellular vesicles for cell-cell signaling.

Mechanosensitive channels are activated by stress in the actin stress fibres, and could be involved in gravity sensing in plants.

Mechanosensitive (MS) channels are expressed in a variety of cells. The molecular and biophysical mechanism involved in the regulation of MS channel activities is a central interest in basic biology. MS channels are thought to play crucial roles in gravity sensing in plant cells. To date, two mechanisms have been proposed for MS channel activation. One is that tension development in the lipid bilayer directly activates MS channels. The second mechanism proposes that the cytoskeleton is involved in the channel activation, because MS channel activities are modulated by pharmacological treatments that affect the cytoskeleton. We tested whether tension in the cytoskeleton activates MS channels. Mammalian endothelial cells were microinjected with phalloidin-conjugated beads, which bound to stress fibres, and a traction force to the actin cytoskeleton was applied by dragging the beads with optical tweezers. MS channels were activated when the force was applied, demonstrating that a sub-pN force to the actin filaments activates a single MS channel. Plants may use a similar molecular mechanism in gravity sensing, since the cytoplasmic Ca(2+) concentration increase induced by changes in the gravity vector was attenuated by potential MS channel inhibitors, and by actin-disrupting drugs. These results support the idea that the tension increase in actin filaments by gravity-dependent sedimentation of amyloplasts activates MS Ca(2+) -permeable channels, which can be the molecular mechanism of a Ca(2+) concentration increase through gravistimulation. We review recent progress in the study of tension sensing by actin filaments and MS channels using advanced biophysical methods, and discuss their possible roles in gravisensing.

Salmonella enterica serotype Paratyphi A carrying CTX-M-15 type extended-spectrum beta-lactamase isolated from a Japanese traveller returning from India, Japan, July 2013.

Emerging drug resistance in Salmonella Typhi and S. Paratyphi is a substantial public health concern. We report what appears to be the first case and isolation of multidrug resistant S. Paratyphi A carrying CTXM-15-type extended-spectrum beta-lactamase from a Japanese traveller returning from India.

228Ra/226Ra ratio and 7Be concentration in the Sea of Japan as indicators for water transport: comparison with migration pattern of Fukushima Dai-ichi NPP-derived 134Cs and 137Cs.

To assess the migration patterns of radiocesium emitted from the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), we analyzed (228)Ra/(226)Ra ratios and (7)Be concentrations and compared them with (134)Cs and (137)Cs concentrations in seawater samples collected within the Sea of Japan before and after the FDNPP accident (i.e., during the period 2007-2012) using low-background γ-spectrometry. The (228)Ra/(226)Ra ratios in surface waters exhibited lateral and seasonal variations, reflecting the flow patterns of surface water. This indicates the transport patterns of the FDNPP-derived radiocesium by surface water. Cosmogenic (7)Be (half-life: 53.3 d) exhibited markedly high concentrations (5-10 mBq/L) at depths shallower than 50 m, with concentrations decreasing steeply (0.2-2 mBq/L) at depths of 50-250 m. The distribution of (7)Be concentrations suggests that the downward delivery of the FDNPP-derived radiocesium to below 50 m depth was negligible for a few months prior to its removal from the Sea of Japan.

High pressure treatment under subfreezing temperature results in drastic inactivation of enveloped and non-enveloped viruses.

Some viruses are sensitive to high pressure. The freeze-pressure generation method (FPGM) applies pressure as high as 250 MPa on a substance, simply by freezing a pressure-resistant reservoir in which the substance is immersed in water. Here we examined whether the FPGM successfully inactivates herpes simplex virus type 1 (HSV-1), an enveloped DNA virus belonging to the human Herpesviridae, and encephalomyocarditis virus (EMCV), an envelope-free RNA virus belonging to the Picornaviridae. After the treatment, HSV-1 drastically reduced the ability to form plaque in Vero cells in vitro as well as to kill mice in vivo. EMCV that had been pressurized failed to proliferate in HeLa cells and induce interferon response. The results suggest that the FPGM provides a feasible procedure to inactivate a broad spectrum of viruses.

Independent risk factors for the co-colonization of vancomycin-resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus in the region most endemic for vancomycin-resistant Staphylococcus aureus isolation.

In the majority of cases of vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant Enterococcus faecalis (VR E. faecalis) served as the vanA donor to S. aureus. Previous studies that evaluated the risk factors for co-colonization with VRE and MRSA did not differentiate between VR E. faecalis and VR E. faecium. This study aimed to identify variables associated with VR E. faecalis and MRSA co-colonization. A retrospective case-control study from January 2008 to December 2009 was conducted at the Detroit Medical Center. Data were extracted from charts and pharmacy records. Unique patients co-colonized with VR E. faecalis and MRSA (defined as isolation of MRSA within 7 days of VR E. faecalis isolation) were compared with patients with VR E. faecalis who were not co-colonized with MRSA. A total of 546 patients with VR E. faecalis isolation were identified. 85 (15.6 %) VR E. faecalis patients were co-colonized with MRSA and 461 (84.4 %) VR E. faecalis patients were not co-colonized with MRSA. The mean age of the study cohort was 65.9 ± 16.4 years, 424 (77.7 %) were African-American, and 270 (49.5 %) were residing in long-term care institutions. Independent predictors of co-colonization of VR E. faecalis and MRSA were male gender, impaired consciousness, ICU stay prior to VR E. faecalis isolation, indwelling devices, and isolation of VR E. faecalis from wounds. MRSA was frequently isolated from the same culture specimen as VR E. faecalis (n = 39, 45.9 %), most commonly from wounds. This large study of patients with VR E. faecalis identified the severity of illness, indwelling devices, and chronic wounds as independent predictors of co-colonization with VR E. faecalis and MRSA.

Neurotransmitters, psychotropic drugs and microglia: clinical implications for psychiatry.

Psychiatric disorders have long and dominantly been regarded to be induced by disturbances of neuronal networks including synapses and neurotransmitters. Thus, the effects of psychotropic drugs such as antipsychotics and antidepressants have been understood to modulate synaptic regulation via receptors and transporters of neurotransmitters such as dopamine and serotonin. Recently, microglia, immunological/inflammatory cells in the brain, have been indicated to have positive links to psychiatric disorders. Positron emission tomography (PET) imaging and postmortem studies have revealed microglial activation in the brain of neuropsychiatric disorders such as schizophrenia, depression and autism. Animal models of neuropsychiatric disorders have revealed the underlying microglial pathologies. In addition, various psychotropic drugs have been suggested to have direct effects on microglia. Until now, the relationship between microglia, neurotransmitters and psychiatric disorders has not been well understood. Therefore, in this review, at first, we summarize recent findings of interaction between microglia and neurotransmitters such as dopamine, serotonin, norepinephrine, acetylcholine and glutamate. Next, we introduce up-to-date knowledge of the effects of psychotropic drugs such as antipsychotics, antidepressants and antiepileptics on microglial modulation. Finally, we propose the possibility that modulating microglia may be a key target in the treatment of various psychiatric disorders. Further investigations and clinical trials should be conducted to clarify this perspective, using animal in vivo studies and imaging studies with human subjects.