Spontaneous recovery from post-COVID-19 brain fog.

Background: One-third of individuals who contract novel coronavirus disease 2019 (COVID-19) reportedly experience persistent symptoms, including respiratory issues, headache, dizziness, taste disorders, fatigue, and various psychiatric and neurological symptoms, known as post-acute sequelae of SARS-CoV-2. In this case report, we present a patient who became aware of brain fog, which is cognitive impairment, approximately 2 months after their COVID-19 symptoms had resolved, accompanied by anxiety and depression. Case Presentation: The patient, a 35-year-old Japanese man, was infected with COVID-19 and resumed work approximately 2 weeks later after symptoms improved. Approximately 1 month after returning to work, the patient's concentration became impaired and he started making noticeable errors at work. These symptoms did not improve, leading him to the outpatient clinic specializing in COVID-19 sequelae at our hospital. Here, he underwent blood tests, electroencephalography, and head magnetic resonance imaging, which did not reveal any abnormalities. Cognitive decline due to COVID-19 sequelae was therefore suspected, prompting his evaluation in our department approximately 5 months after his initial COVID-19 infection. Detailed cognitive function tests were performed. He was monitored without the use of medications, and his cognitive function gradually improved. Approximately 11 months after his initial COVID-19 infection, the same cognitive function tests were conducted again, because his subjective cognitive function symptoms had disappeared, and improvement was observed in many items. Conclusion: Since brain fog is a relatively common sequela, we emphasize the importance of keeping this in mind from the initial consultations and comparing results over time.

Trends and Characteristics of Suicide-Related Behaviors Before and After the COVID-19 Epidemic in Tottori, Japan: A Retrospective Study.

Background: In Japan, the number of suicides has increased since the coronavirus disease (COVID-19) epidemic. However, only a few studies have examined the trends among individuals who attempted suicide. In this study, we examined the background characteristics and motives of individuals who attempted suicide and visited the emergency room because of suicide-related behavior before and after the spread of COVID-19. Methods: This single-center retrospective observational study collected information from electronic medical records. We included patients who presented to the emergency department of Tottori University Hospital with suicide-related behaviors between May 1, 2017, to August 31, 2022. The period from May 1, 2017, through December 31, 2019, was designated as 'the period before COVID-19" (before-period), and that from January 1, 2020, through August 31, 2022, was designated as "the period after COVID-19" (after-period). We compared the total number of cases, their background, and motives for suicide-related behaviors between the before- and after-periods. Results: The total number of suicide events was 304. Of these, 182 and 122 occurred during the before-period and after-period, respectively. The incidence of the F3 category of the International Classification of Diseases, 10th Revision, increased, while that of the F4 and F6 categories decreased during the after-period. The proportion of suicide attempts due to health problems decreased and that of work problems increased during the after-period. Conclusion: The total number of suicide-related behaviors decreased after the COVID-19 pandemic. This may be because patients with psychiatric disorders other than depression and schizophrenia often engage in suicidal behavior through non-fatal methods, such as drug overdose and wrist-cutting, which may have led them to refrain from seeing a doctor. The proportion of suicidal motivation due to work-related fatigue has increased, perhaps because the quality and quantity of work changed significantly due to COVID-19.

Performing a sperm DNA fragmentation test in addition to semen examination based on the WHO criteria can be a more accurate diagnosis of IVF outcomes.

BACKGROUND: We analyzed the sperm DNA fragmentation index (DFI) and general semen test based on the World Health Organization (WHO) criteria and compared the two tests using semen factors. In addition, we examined whether DFI is a reliable parameter associated with in vitro fertilization (IVF) outcomes. METHODS: Sperm chromatin dispersion (SCD) and general semen tests were conducted in accordance with the WHO 2010 guidelines, and correlations between the two tests were investigated. The WHO criteria were set as the cutoff values for each of the following factors: semen volume, concentration, total sperm count, motility, and normal morphology, and compared with the DFI results. RESULTS: The subjects had a mean sperm DFI of 15.3% ± 12.6%, and the DFI increased with age. In contrast, motility and normal morphology decreased as the DFI increased. Patients who satisfied the WHO criteria in terms of concentration, total sperm count, and motility had a significantly lower DFI than those who did not satisfy the criteria. Therefore, evaluation with a general semen test based on the WHO criteria should be regarded as a qualitative evaluation of all factors other than semen volume and normal morphology. CONCLUSIONS: High DFI (≥ 30%) caused a low blastocyst development rate following intracytoplasmic sperm injection. Male infertility due to DFI should be suspected when IVF results are poor despite normal semen findings based on the WHO criteria. The results of this study suggest that the SCD test may more accurately evaluate the correlation between IVF clinical outcomes and male infertility. Therefore, it is important to focus on DFI measurements.

Comparative efficacy and safety of suvorexant and lemborexant for insomnia treatment.

Aim: Although suvorexant and lemborexant, which have orexin receptor antagonist activity, are used as sleep medications in Japan, no report has directly compared their efficacy and safety. This study compared the efficacy and safety of the drugs. Methods: This retrospective cohort study included patients who presented to the Outpatient Department of Psychiatry at Tottori University Hospital between December 1, 2020, and December 31, 2021. Information was obtained from 108 patients who were newly treated with suvorexant or lemborexant. Data were analyzed after excluding one case of discontinuation due to a post-administration allergic reaction. Improvement in sleep status after administration was assessed retrospectively from medical records by using the Clinical Global Impressions-Improvement (CGI-I) Scale, which is a subscale of the Clinical Global Impressions (CGI) Scale. The incidence of side-effects was obtained from the medical records of the patient's first visit after administration. Results: There was no significant difference between the CGI-I scores in the suvorexant (mean [SD], 3.05 [0.93]) and lemborexant groups (mean [SD], 3.38 [0.83]) (p = 0.10). The incidence of side-effects with continued treatment was not significantly different between the suvorexant group (12.5%) and the lemborexant group (2.9%) (p = 0.10). Patients who switched from suvorexant to lemborexant had CGI-I scores ≤4, and no side-effects were observed after switching to lemborexant. Conclusion: There was no difference in effectiveness between suvorexant and lemborexant. However, lemborexant might cause side-effects less frequently than suvorexant, at least in the early stages of treatment.

Actual conditions of person-to-object contact and a proposal for prevention measures during the COVID-19 pandemic.

This study focused on human contact behavior with objects and discussed countermeasures during the COVID-19 pandemic across 15 location types. Reducing contact with objects and disinfecting items can be implemented at a relatively low cost. We created a protocol for organizing the objects, and 1260 subjects who went outside during a day between December 3-7, 2020 in Tokyo and Kanagawa, Japan were surveyed. The participants touched 7317 objects in total; the most common objects were doors, chairs, baskets, elevator equipment, and cash. One-way analysis of variance and Scheffé's multiple comparison test showed that supermarkets had the lowest mean and median values despite having the highest number of users, contact objects, and object types. Conversely, the values for hotels were the highest, significantly higher than that for other places, excluding amusement parks, workplaces, and schools and universities. Furthermore, the long-tailed frequency distribution of the number of objects suggests that the objects touched by many individuals are limited; thus, it is important to determine the objects to be prioritized for disinfection at each location. The data and protocol could inform infection countermeasures that properly address the contact realities as they pertain to people's behavior and objects.

Net-TF-SW: Event Popularity Quantification with Network Structure.

Event popularity quantification is essential in the determination of current trends in events on social media and the internet. Particularly, it is important during a crisis to ensure appropriate information transmission and prevention of false-rumor diffusion. Here, we propose Net-TF-SW - a noise-robust and explainable topic popularity analysis method. This method is applied to tweets related to COVID-19 and the Fukushima Daiichi Nuclear Disaster, which are two significant crises that have caused significant anxiety and confusion among Japanese citizens. The proposed method is compared to existing methods, and it is verified to be more robust with respect to noise.

Intracerebroventricular administration of leptin increases anxiety-like behavior in female rats after semi-starvation--implications for anxiety in eating disorders.

BACKGROUND: Patients with eating disorders often exhibit abnormal eating conditions like food restriction, adipocyte and body weight reduction, and pathologic anxiety-like behavior. The role of leptin, which is recognized as an adipocyte-derived hormone, on anxiety-like behavior in eating disorders is still unclear. METHODS: We investigated the role of leptin on anxiety-like behavior with or without semi-starvation using the elevated plus-maze test in adolescent female rats. In our first experiment, anxiety-like behavior was evaluated with the elevated plus-maze test 30 min after intracerebroventricular administration of 3 microg of leptin or vehicle. In our second experiment, the rats were allowed access to food for only 2 hr each day for 7 days. Then, leptin or vehicle was administered to the rats after the last 2 hr feeding period, and anxiety-like behaviors were evaluated in the same way as in the first experiment. RESULTS: In the first experiment, there was no difference between the anxiety-like behaviors observed after leptin administration and those seen after vehicle administration. Under the conditions of semi-starvation, however, the percentage of time spent in the open arms in the rats given leptin was lower than that in rats given vehicle. CONCLUSIONS: These results suggest that leptin administration causes anxiety-like behavior only after semistarvation. Leptin might play an important role in pathologic anxiety-like behavior in eating disorders.

Effects of the nonsugar fraction of brown sugar on chronic ultraviolet B irradiation-induced photoaging in melanin-possessing hairless mice.

Brown sugar has been used traditionally for the treatment of skin trouble as a component of soaps or lotions. Symptoms of aging including wrinkles and pigmentation develop earlier in sun-exposed skin than unexposed skin, a phenomenon referred to as photoaging. Ultraviolet B (UVB) radiation is one of the most important environmental factors influencing photoaging. The aim of this study was to clarify whether the nonsugar fraction of brown sugar prevents chronic UVB-induced aging of the skin using melanin-possessing hairless mice. The nonsugar fraction (1% or 3% solution, 50 mul/mouse) was applied topically to the dorsal region every day for 19 weeks. Both solutions prevented an increase in skin thickness and reduction in skin elasticity caused by the UVB. The 3% solution also prevented wrinkles and melanin pigmentation as well as increases in the diameter and length of skin blood vessels. Increases in the expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in UVB-irradiated skin was inhibited by the nonsugar fraction. Prevention of UVB-induced aging of the skin by topical application of the nonsugar fraction of brown sugar may be due to inhibition of increases in MMP-2 and VEGF expression.

Analysis of skin disposition and metabolism of ethyl nicotinate after topical application using dual agar gel disc-inserted rats.

The skin disposition and metabolism of topically applied ethyl nicotinate (EN) were evaluated in dual agar gel disc-inserted hairless rats, which have two agar gel discs subcutaneously inserted into the abdominal region as drug receptors, and a topical formulation containing EN placed on either side of the gel disc through the skin. Plasma and agar levels of EN and its metabolite, nicotinic acid (NA), were followed every 2 h over 6 h. EN permeated through the skin barrier and partly metabolized to NA with 89.4% of the metabolite ratio [NA/(EN+NA)] at 6 h. Some EN and NA in the skin moved to the systemic circulation, and the remainder migrated into the agar gel below the formulation. The total amount (EN+NA) in the skin that distributed from the formulation directly to the systemic circulation and the application side of the gel corresponded to 95.2% and 4.8% of the total skin permeation at 6 h, respectively. Only NA was distributed from the systemic circulation to both agar gel discs. The NA fraction in the application side of the gel from the circulation was only 1% of the total amount in the agar gel. The metabolite ratio on the application side of the agar gel was higher than that in the receiver for the in vitro skin permeation using excised hairless rat skin. This difference was probably related to a lower EN ratio in viable skin in situ than in vitro. These results suggest that the present in situ method is useful to evaluate the skin disposition and metabolism of topically applied drugs.

Analysis of skin disposition of flurbiprofen after topical application using dual agar gel discs-inserted rats.

Most of the drug fraction penetrating the skin after topical application is taken up by the cutaneous blood flow, although the rest directly migrates into deeper tissues such as the subcutis and muscle. A new in situ experimental hairless rat model was designed to distinguish these fractions of topically applied drugs. Flurbiprofen, a non-steroidal anti-inflammatory drug, was selected as the model drug. In this model, two agar gel discs were subcutaneously inserted into the abdominal region of hairless rats as a drug receptor, and a topical formulation containing the drug was placed above either side of the gel disc. Plasma and agar levels of flurbiprofen were followed every 2 h over 10 h. The migration fraction of the drug into the systemic circulation and that directly to subcutaneous tissues were calculated to be 99.8% and 0.2% against the total amount which penetrated the skin, and the drug ratios into agar gel from the systemic circulation and not from the systemic circulation (i.e. directly migrated from the formulation) were 16.0% and 84.0%, respectively, at 10 h. This in situ drug disposition profile in skin was similar to the in vivo profile calculated from the in vivo muscle amount of flurbiprofen using muscle clearance. These results clearly suggest that the present in situ experimental model is a valuable tool for easy analysis of the skin disposition of topically applied drugs.

Corticotropin-releasing factor receptor type 1, but not type 2, in the ventromedial hypothalamus modulates dopamine release in female rats.

Corticotropin-releasing factor (CRF) plays an important role in stress responses and is mediated through two subtypes of receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Each CRF receptor might have a different function through several neurotransmitter systems; however, the mechanism remains unclear. To clarify the role of each receptor in dopamine (DA) metabolism, we measured the change of extracellular concentrations of DA and the metabolites in the ventromedial hypothalamus (VMH) that played important roles in the stress response of freely moving female rats in response to the direct administration of comparative CRFR1 selective agonist, CRF, or CRFR2 selective agonist, Urocortin II (Ucn II), into the brain region. Administration of 10 microg CRF increased extracellular concentrations of DA compared with 2 microg CRF immediately after injection, and this effect was not observed after 60 min of 10 microg CRF injection. On the other hand, this change did not always occur after Ucn II administration. These results suggest that the activation of CRFR1, but not CRFR2, modulates the release of DA in VMH.

[Neuroendocrine differentiation in adenocarcinoma of prostate during combined androgen blockade therapy: a case report].

Prostatic neuroendocrine (NE) carcinoma is a rare disease with a poor prognosis because of its rapid progression and the androgen-independent characteristic, for which no successful therapy is available presently. We report a case of NE differentiated prostate cancer, which was diagnosed as adenocarcinoma initially and progressed with NE differentiation during the combined androgen blockade therapy.

Utility of a three-dimensional cultured human skin model as a tool to evaluate the simultaneous diffusion and metabolism of ethyl nicotinate in skin.

The simultaneous diffusion and metabolism of ethyl nicotinate (EN) in a cultured human skin model, Living Skin Equivalent-high, was evaluated by the in vitro skin permeation and metabolism experiments, and esterase distribution was also determined. Theoretical calculations using Fick's 2nd Law of Diffusion with Michaelis-Menten kinetics were performed to obtain the permeation and metabolic parameters together with information on enzyme distribution. The obtained data was compared with the corresponding results in excised hairless rat skin. The partition coefficient of EN from the vehicle to the skin was of the same order of magnitude for the cultured human skin and hairless rat skin, but the diffusion and metabolic parameters were different. Esterase concentration in the epidermal membrane was greater than in the dermis of cultured skin, which was similar to hairless rat skin. Taking into account the similarities and differences between the membranes, the cultured human skin model can be utilized as a model membrane to rapidly predict simultaneous diffusion and metabolism of the prodrug through human skin.

Differences in oligosaccharide pattern of a sample of polar bear colostrum and mid-lactation milk.

Although the concentrations of carbohydrate in the colostrum and in the mid-lactation milk of polar bear (Ursus maritimus) were similar, the oligosaccharide patterns differed. The colostrum sample contained Neu5Ac(alpha2-3)Gal(beta1-4)Glc (3'-N-acetylneuraminyllactose), GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)Glc (A-tetrasaccharide), Fuc(alpha1-2)Gal(beta1-4)Glc (2'-fucosyllactose) and Gal(beta1-4)Glc (lactose). The mid-lactation milk contained Gal(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)[Fuc(alpha1-3)]Glc (B-pentasaccharide), GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)[Fuc(alpha1-3)]Glc (A-pentasaccharide), Gal(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)Glc (B-tetrasaccharide), A-tetrasaccharide, Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1-3)]Glc (3-fucosylisoglobotriose), Gal(alpha1-3)Gal(beta1-4)Glc (isoglobotriose) and lactose. The dominant saccharides in the colostrum were 3'-N-Acetylneuraminyllactose and lactose, whereas isoglobotriose was the dominant saccharide in the mid-lactation milk in which lactose was only a minor component. Isoglobotriose, which had previously been found to be a dominant saccharide in mature milk from the Ezo brown bear, the Japanese black bear and the polar bear, was not found in the polar bear colostrum.