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The present study aimed to verify the effect of bilateral intra-hippocampus administration of the neurosteroid allopregnanolone (3α-hydroxy-5α-pregnan-20-one; 3α, 5α-THP) in the forced swimming test (FST) and in the α4 and γ2 GABAA receptor subunits gene expression. Results showed that bilateral intra-hippocampal allopregnanolone administration of 2.5μg/rat (P < 0.05) reduced immobile behavior and increased climbing behavior in the FST. Overall, for all doses of allopregnanolone tested (1.25, 2.5, 5.0μg/rat), an increase of γ2 (P < 0.05) GABAA subunit mRNA was observed. There was a higher increase in the γ2 gene expression in the right hemisphere than in the left hemisphere (P < 0.01) after allopregnanolone treatment. Intra-hippocampal allopregnanolone did not change the expression of the α4 subunits. In conclusion, intra-hippocampal administration of allopregnanolone produces an antidepressant-like effect in the FST at an intermediate dose, confirming the potential of neurosteroids as a new class of antidepressant drugs. Our findings suggest that the γ2, but not the α4 GABAA subunit, needs further evaluation to be involved in the antidepressant effect of allopregnanolone in the hippocampus and that there is a hemispheric diversity in the biochemical effect of the drug. [ABSTRACT FROM AUTHOR]

Human identity is a complex process linked to the subject and his environment, both constantly evolving. Personality is developed and changed throughout lifetime, but it has a core that remains constant.

Introduction: The use of herbal medicines for the promotion of healing and maintenance of health has becoming popular throughout the world. Herbal medicine preparations are often regarded as being safe and harmless due to their natural origin, many of which are taken with or without a physician's prescription. A number of these products were found to be adulterated with synthetic modern drugs as well as heavy metals. To identify toxic and adulterated substances in herbal products commonly available in the Malaysian market, 83 samples of such products were analyzed. Methodology: Samples (pills, powders, liquids, pastilles, capsules, and tablets) received between January 2004 to February 2007 from hospitals, clinics, manufacturers, distributors and others were extracted and analyzed by either gas or liquid chromatograph using Mass Spectrometer or Tandem Mass Spectrometer respectively. The identification of adulterants was based on mass spectral matching with positive reference standards or those substances in NIST and Wiley libraries. Heavy metals were detected using Atomic Absorption Spectrometer. As quality control measures, specimen, blank and positive control samples were run together. Results: It was found that 39.7 % of the herbal products tested were adulterated with a maximum number of five adulterants in one herbal product. By dosage form, the adulteration rate was the highest in liquids (66.7 %), followed by powders (50.0 %), capsules (26.9 %) and tablets (25.0 %). Forty (40) drugs not listed on product labels were identified in the herbal products, examples of which are: sibutramine, chlorpheniramine, betamethasone, chlorzoxazone, indomethacin, and ethenzamide. Heavy metals such as lead, cadmium, arsenic and mercury were detected within permissible limit. Conclusion: The adulteration of herbal products available in local market is high. The adulterants include dangerous and toxic chemical compounds. National Pharmaceutical Control Bureau should be more stricter in registering herbal products and post surveillance studies should be frequently conducted to ensure all manufacturers follow the established guidelines. [ABSTRACT FROM AUTHOR]

Introduction: The humoral response after SARS-CoV-2 vaccination and boosters in kidney transplant recipients (KTRs) is heterogeneous and depends on immunosuppression status. There is no validated immune measurement associated with serological response in clinical practice. Multicolor flow cytometric immunophenotyping could be useful for measuring immune response. This study aimed to study B- and T-cell compartments through Standardized EuroFlow PID Orientation after SARS-CoV-2 vaccination and their association with IgG SARS-CoV-2 seropositivity status after two doses or boosters., Methods: We conducted a multicenter prospective study to evaluate humoral response after SARS-CoV-2 vaccination in KTRs. Heterologous regimen: two doses of inactivated SARS-CoV-2 and two boosters of BNT162b2 mRNA (n=75). Homologous vaccination : two doses of BNT162b2 mRNA and one BNT162b2 mRNA booster (n=13). Booster doses were administrated to KTRs without taking into account their IgG SARS-CoV-2 seropositivity status. Peripheral blood samples were collected 30 days after the second dose and after the last heterologous or homologous booster. A standardized EuroFlow PID Orientation Tube (PIDOT) and a supervised automated analysis were used for immune monitoring cellular subsets after boosters., Results: A total of 88 KTRs were included and divided into three groups according to the time of the first detected IgG SARS-CoV-2 seropositivity: non-responders (NRs, n=23), booster responders (BRs, n=41), and two-dose responders (2DRs, n=24). The NR group was more frequent on mycophenolate than the responder groups (NRs, 96%; BRs, 80%; 2DRs, 42%; p=0.000). Switched memory B cells in the 2DR group were higher than those in the BR and NR groups (medians of 30, 17, and 10 cells/ul, respectively; p=0.017). Additionally, the absolute count of central memory/terminal memory CD8 T cells was higher in the 2DR group than in the BR and NR groups. (166, 98, and 93 cells/ul, respectively; p=0.041). The rest of the T-cell populations studied did not show a statistical difference., Conclusion: switched memory B cells and memory CD8 T-cell populations in peripheral blood were associated with the magnitude of the humoral response after SARS-CoV-2 vaccination. Boosters increased IgG anti-SARS-CoV-2 levels, CM/TM CD8 T cells, and switched MBCs in patients with seropositivity after two doses. Interestingly, no seropositivity after boosters was associated with the use of mycophenolate and a lower number of switched MBCs and CM/TM CD8 T cells in peripheral blood., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Seija, García-Luna, Rammauro, Brugnini, Trías, Astesiano, Santiago, Orihuela, Zulberti, Machado, Recalde, Yandián, Guerisoli, Noboa, Orihuela, Curi, Bugstaller, Noboa, Nin, Bianchi, Tiscornia and Lens.)

Background: Antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA or adenoviral vector-based vaccines is weak in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines in KT. Here, we compare antibody response following vaccination with inactivated virus (CoronaVac®) and BNT162b2 mRNA., Methods: A national multicentre cross-sectional study was conducted. The study group was composed of patients from all KT centres in Uruguay, vaccinated between 1 and 31 May 2021 (CoronaVac®, n = 245 and BNT162b2, n = 39). The control group was constituted of 82 healthy individuals. Participants had no prior confirmed coronavirus disease 2019 (COVID-19) test. Blood samples were collected between 30 and 40 days after the second dose. Serum-specific immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein were determined using the COVID-19 IgG QUANT ELISA Kit., Results: Only 29% of KT recipients showed seroconversion (36.5% BNT162b2, 27.8% inactivated virus, P = 0.248) in comparison with 100% in healthy control with either vaccine. Antibody levels against RBD were higher with BNT162b mRNA than with inactivated virus [median (interquartile range) 173 (73-554) and 29 (11-70) binding antibody units (BAU)/mL, P < 0.034] in KT and 10 times lower than healthy control [inactivated virus: 308 (209-335) and BNT162b2: 2638 (2608-3808) BAU/mL, P < 0.034]. In multivariate analysis, variables associated with negative humoral response were age, triple immunosuppression, estimated glomerular filtration rate and time post-KT., Conclusion: Seroconversion was low in KT patients after vaccination with both platforms. Antibody levels against SARS-CoV-2 were lower with inactivated virus than BNT162b mRNA. These findings support the need for strategies to improve immunogenicity in KT recipients after two doses of either vaccine., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR < 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.

Background: Current consensus recognizes the benefits of early intervention in palliative care consultation teams (PCCTs). As consultants, we should now attempt to improve the quality of our teams by utilizing a method mainly used in the business field. We aimed to investigate the effects of iterative evaluation of customer satisfaction surveys, filled by physicians and ward nurses in this study, for quality improvement of PCCTs., Methods: In October 2019, the participants filled the first questionnaire survey about palliative care and PCCTs at a 678-bed hospital, and improvement areas were uncovered. Refinements were planned and implemented, and then reevaluated using the second questionnaire survey in March 2020., Results: In addition to the characteristics of our clients evaluated from approximately 500 valid responses, the first survey showed that the response rate of the questionnaire, knowledge of palliative care and PCCTs, and publicity of the PCCT were recognized as issues needing attention. We planned to contrive ways to collect questionnaires, hold monthly workshops for palliative care, launch newsletters of palliative care, and go on client rounds. The second survey revealed improvements in the physicians' response rate (p = 0.02), the accuracy rate of application of PCCTs in Japan (p < 0.01), and ward nurses' confidence in opioid use (p = 0.04) and tendency toward easier accessibility to the PCCT (p = 0.07)., Conclusion: Continual quality improvements through iterative, customer satisfaction survey-driven evaluation are a widely established practice in the business field. By using this appropriately, we could enable PCCTs to improve their quality.

Animal models show that cocaine sensitization, a behavioral marker of addiction, is more significant in intact gonadal female than male rats and ovariectomy suppress this behavior in female rats. However, few studies explore changes in neurotransmission related to this phenomenon. Here we investigated the in vivo changes on GABA, glutamate, and taurine levels in the medial prefrontal cortex (mPFC) of gonadal intact or ovariectomized female rats after a cocaine challenge administration. Adult female rats were bilaterally ovariectomized (OVX), or sham-operated (SHAM) and randomly assigned to control (CTR), acute (ACT), or repeated (RPT) cocaine administration groups. In the challenge day, after eight days of daily cocaine (15 mg/kg) or saline administration and ten days of washout and stereotaxic surgery, RPT and ACT groups received cocaine, and the CTR group received saline. Horizontal locomotion was monitored concomitantly with microdialysate collection to determine extracellular GABA, glutamate, and taurine levels. Hormonal determination in blood samples confirmed the lower hormonal status of the OVX. Cocaine sensitization occurred in SHAM-RPT female rats after the challenge administration. Non-sensitized OVX-RPT rats showed a peak of GABA at 30 min after cocaine administration, with no change on glutamate and taurine levels. Therefore, elevated GABA levels in the mPFC and lower serum estrogen levels abolish cocaine sensitization behavior in ovariectomized female rats. We discuss some possible implications of these finding for future models of cocaine sensitization research lighting in the female hormonal influence., (Copyright © 2020. Published by Elsevier B.V.)

Five-aminolevulinic acid, an amino acid that is metabolized in the cytoplasm to become protoporphyrin IX, is used in photodynamic diagnosis in various carcinomas because it accumulates in higher concentrations in tumor tissue than in normal tissue. 5-Aminolevulinic acid-induced fluorescent urine cytology is more sensitive than conventional urine cytology only in low grade urothelial carcinoma (UC), but it showed a tendency for higher sensitivity in high grade UC. To increase the number of patients and reconsider our previous findings, we compared the sensitivity and specificity of preoperative urine cytology and fluorescent urine cytology in 343 patients diagnosed as having UCs pathologically (215 bladder cancers, 128 upper tract UCs) and 197 non-cancer patients at Osaka Rosai Hospital from March 2013 to December 2019. The sensitivities of fluorescent urine cytology and conventional urine cytology were 81.1% and 63.3% (p<0.001), respectively, and specificities were 92.9% and 93.9% (p=0.84), respectively. The sensitivity of fluorescent urine cytology was superior to that of conventional urine cytology in both low grade UC (76.8% vs 41.1%, p<0.001) and high grade UC (83.1% vs 74.0%, p=0.023).

Objectives: To investigate the efficacy of selective upper tract urinary cytology using extracorporeal 5-aminolevulinic acid for the diagnosis of upper urinary tract urothelial carcinoma., Methods: We evaluated 104 patients who underwent radical nephroureterectomy and were diagnosed pathologically as having upper urinary tract urothelial carcinoma between March 2013 and May 2019 in Osaka Rosai Hospital. Preoperatively, we collected upper tract urinary cytology from both sides, and compared the sensitivity and specificity between conventional urine cytology and 5-aminolevulinic acid-induced fluorescent urine cytology., Results: The sensitivity of 5-aminolevulinic acid-induced fluorescent selective upper tract urinary cytology was significantly higher than conventional cytology (90.4% vs 66.3%, P < 0.001), whereas the specificity was equally high (100% vs 98.2%, P = 1.0). In more detailed analysis, the sensitivity of 5-aminolevulinic acid-induced fluorescent selective upper tract urinary cytology was significantly higher than that of conventional cytology unrelated to patients' age (<76 years: 90.2% vs 68.6%, P = 0.013; ≥76 years: 90.6% vs 64.2%, P = 0.021), sex (male: 89.2% vs 67.5%, P = 0.001; female: 95.2% vs 61.9%, P = 0.02) or pT stage (pT1 or less: 91.4% vs 69.0%, P = 0.005; pT2 or more: 89.1% vs 63.0%, P = 0.006), tumor grade (high grade: 91.0% vs 70.5%, P = 0.002; low grade: 88.5% vs 53.8%, P = 0.013), and tended to be more efficacious for tumors that could not be detected by imaging techniques (83.3% vs 50.0%, P = 0.075)., Conclusions: 5-Aminolevulinic acid-induced fluorescent selective upper tract urinary cytology is more sensitive than conventional cytology for the diagnosis of upper urinary tract urothelial carcinoma, regardless of pT stage and tumor grade., (© 2020 The Japanese Urological Association.)

The patient was a 43-year-old man. At 30 years of age, he underwent high-inguinal orchiectomy for a right testicular tumor and was diagnosed with seminoma pT1N0M0. The patient had been followed without additional treatment and had dropped out 7 years after surgery. At 43 years of age, abdominal ultrasonography performed for screening revealed a swollen 4 cm-wide intra-abdominal lymph node, and he was referred to our department. Abdominal contrast-enhanced computed tomography (CT) showed a mass with a 5 cm-wide contrast effect that contacted the anterior surface of the inferior vena cava from the duodenum to the aortic bifurcation. Histological examination by trans-duodenal ultrasound-guided fineneedle aspiration suggested late recurrence of seminoma. After receiving three courses of BEP (bleomycin, etoposide, and platinum) therapy, the patient underwent laparoscopic lymphadenectomy. Pathological examination showed no residual tumor, and the patient was free of recurrence at 13 months after surgery.

Background: Little is known about the potential use of the eosinophil count as a predictive marker of bloodstream infection. In this study, we aimed to assess the reliability of eosinopenia as a predictive marker of bloodstream infection., Methods: This retrospective cohort study was performed in the outpatient department and general internal medicine department of a tertiary university hospital in Japan. A total of 189 adult patients with at least 2 sets of blood cultures obtained during the period January 1-December 31, 2018, were included; those with the use of antibiotic therapy within 2 weeks prior to blood culture, steroid therapy, or a history of haematological cancer were excluded. The diagnostic accuracies of each univariate variable and the multivariable logistic regression models were assessed by calculating the areas under the receiver operating characteristic curves (AUROCs). The primary outcome was a positive blood culture indicating bloodstream infection., Results: Severe eosinopenia (< 24.4 cells/mm 3 ) alone yielded small but statistically significant overall predictive ability (AUROC: 0.648, 95% confidence interval (CI): 0.547-0.748, P < 0.05), and only moderate sensitivity (68, 95% CI: 46-85%) and specificity (62, 95% CI: 54-69%). The model comprising baseline variables (age, sex), the C-reactive protein level, and neutrophil count yielded an AUROC of 0.729, and further addition of eosinopenia yielded a slight improvement, with an AUROC of 0.758 (P < 0.05) and a statistically significant net reclassification improvement (NRI) (P = 0.003). However, the integrated discrimination index (IDI) (P = 0.284) remained non-significant., Conclusions: Severe eosinopenia can be considered an inexpensive marker of bloodstream infection, although of limited diagnostic accuracy, in a general internal medicine setting.

Fever is one of the most common symptoms seen in patients. The work-up and follow-up of fever in an outpatient-only setting is a reasonable option for stable patients referred for unexplained fever; however, the safety and efficacy of outpatient follow-up for those patients remain unclear. We conducted this study to evaluate the safety and efficacy of outpatient follow-up for referred patients with unexplained fever.This study was a retrospective cohort study. We included patients referred to the outpatient department of the diagnostic medicine of our university hospital for unexplained fever between October 2016 and September 2017. Exclusion criteria were recurrent fever or admission for fever evaluation prior to referral. Main outcomes of interest were the rate of admission without diagnosis, rate of remission of fever, and the total duration of fever in undiagnosed patients.Among 84 patients included in this study, 17 (20%) were diagnosed during outpatient follow-up, 6 (7%) were admitted due to worsened condition, 5 (6%) were lost to follow-up, and 56 (67%) were followed up as outpatients without a diagnosis. Among the 56 undiagnosed patients, fever resolved in 53 during outpatient follow-up with or without treatment (95%). The total duration of resolved fever in undiagnosed patients was within 8 weeks.Follow-up of patients referred for unexplained fever in an outpatient setting is safe and effective.

Background: Somatization is regarded as psychological or emotional distress in the form of physical symptoms that are otherwise medically unexplained., Case Presentation: We report a case of a patient with a somatic symptom disorder (SSD) and depression who was later diagnosed with anterior cutaneous nerve entrapment syndrome (ACNES) when Carnett's test was positive and block anesthesia using trigger point injections dramatically improved the symptom of abdominal pain., Conclusion: We concluded that the differentiation of SSDs, such as psychogenic pain, from ACNES is very difficult. Psychiatrists should be aware of this syndrome.

Background: In general, urine cytology is often problematic because of its low sensitivity, especially for low-grade urothelial carcinoma (UC) in clinical practice. To improve the sensitivity, we focused on 5-aminolevulinic acid (5-ALA), because recent studies suggested that 5-ALA-induced urine cytology can be used for photodynamic diagnosis. In this study, we evaluated the diagnostic efficacy of 5-ALA-induced fluorescent urine cytology for UC., Methods: We included in this study 318 patients comprising 158 non-cancer patients, 84 bladder tumor patients, and 76 upper urinary tract urothelial carcinoma (UUT-UC) patients treated in our institution from March 2013 to September 2018. Using the same voided urine sample, we compared sensitivity and specificity between conventional urine cytology and 5-ALA-induced fluorescent urine cytology., Results: Overall, the sensitivity of 5-ALA-induced fluorescent urine cytology was significantly higher than that of conventional urine cytology (86.9% vs. 69.4%; p = 0.0002), and the specificity was equivalently high (96.2% vs. 95.6%; p = 1.0). In subgroup analysis, the high sensitivity of 5-ALA-induced fluorescent urine cytology was also detected regardless of age, sex, and tumor type. However, in terms of stage and grade, differences were only detected in patients with less than pTa stage (89.2% vs. 52.1%; p = 0.0001) and low-grade tumor (91.5% vs. 51.1%; p < 0.0001)., Conclusions: 5-ALA-induced fluorescent urine cytology was significantly more effective for UC diagnosis when compared with the conventional cytology, especially in patients with low-stage and low-grade tumors. These findings indicate that 5-ALA-induced fluorescent urine cytology may potentially be a very useful tool for clinical use.

(Purpose) We reviewed 207 patients with urinary dysfunction who were managed by voiding care team at Osaka Rosai Hospital between November 2016 and June 2018. (Materials & methods) The study involved 112, 32, 24, 19, 10, 7, and 3 patients in the Urology, Orthopedics, Surgery, Internal Medicine, Neurosurgery, and Otorhinolaryngology departments, respectively. The average age was 72.7 years, ranging from 27 to 94 years, and the patients were170 males and 37 females. The average body mass index was 23.3, ranging from 11.6 to 43.7. The degree of activity of daily life (ADL) was distributed from J (independent ADL) to C (bedridden), and consisted of 132 in J category, 23 in A, 28 in B, 24 in C. Forty-seven patients had diabetes mellitus (DM), 36 had a cranial nerve disease, 25 had a history of urinary retention, 17 had indwelling urethral catheters on admission, 53 had an emergency hospital admission, and 174 underwent ≥1 operations during admission. (Results & conclusions) Among the 112 patients treated in the Urology department, 60 underwent robot-assist radical prostatectomy (RARP), 36 transurethral resection of prostate (TUR-P) and Holmium laser enucleation of the prostate (HoLEP), and 16 other procedures. A total of 93% were indwelling urethral catheter free, and 92% were pad-free (≤1 pad per day) at 1 year. In contrast, only 66% of the 95 patients in other departments were indwelling urethral catheter free at 1 year and were indwelling urethral catheter-free within 100 days, except for only one patient. The self-reliant voiding rate, including patients who have their indwelling urethral catheter removed or managed clean intermittent self-catheterization, was 91% at 1 year. A univariate analysis indicated that an ADL of J, independent ambulation, self-care/undiapered, self-reliant voiding score ≤4 (on a scale from 0 to 10, with higher score indicating a poorer ADL), and a urinary function ≤4 (on a scale from 0 to 10, with a higher score indicating greater urinary dysfunction) were significantly associated with freedom from urethral catheter. A multivariate analysis with Cox's proportional hazard model revealed a urinary function of ≤4 to be an independent good prognosticator for being catheter-free. Furthermore, a univariate analysis indicated that ADL J, a scheduled hospital admission, ≥1 operations during admission, independent ambulation, self-care/independent portable toilet, self-care/undiapered, self-reliant voiding score (≤4), and a urinary function of ≤4 were significantly associated with the acquisition of self-reliant voiding. A multivariate analysis with Cox's proportional hazard model revealed a self-reliant voiding of ≤4 to be an independent good prognosticator for self-reliant voiding. (Conclusions) Achieving freedom from an indwelling urethral catheter and acquiring a self-reliant voiding function are suggested to be very important for integrated urinary care.