Safety assessment of L-Arg oral intake in healthy subjects: a systematic review of randomized control trials.

L-Arg is a nonessential amino acid but has many physiological roles. Accordingly, L-Arg has been used in various fields, but there is only limited information available about its safety upon overdose. Generally, the no-observed adverse effect level (NOAEL) is used when setting the upper amount for chemical substances. Recently, systematic reviews have been used to assess the safety as well as the effectiveness and usefulness of them. Therefore, we conducted an assessment of the safety of the oral intake of L-Arg in healthy subjects using gastrointestinal symptoms as an index. We limited the study design to only double-blind randomized controlled trials and searched PubMed, Cochrane Library, EBSCOhost, and Ichushi-Web from inception until May 2021. Assessment of the quality of studies was conducted using the Cochrane Collaboration tool and Jadad score, and the random effects model was used for data analysis. Ultimately, 34 studies were selected for inclusion in this work. The dosage of L-Arg used in the studies ranged from 2000 to 30,000 mg/day (or/one-time dose), and the treatment duration was 1-84 days. The increased risk of gastrointestinal symptoms associated with L-Arg intake from 23 studies (647 participants in total) in which such symptoms were reported was 0.01 (95% confidence interval: - 0.02-0.04), which was not significant difference. NOAEL was estimated as 7531 mg/ one-time dose using a weighted change-point regression model (UMIN000046133).Registration and protocol: Umin.ac.jp as UMIN000046133.

Early Probiotic Supplementation of Healthy Term Infants with Bifidobacterium longum subsp. infantis M-63 Is Safe and Leads to the Development of Bifidobacterium-Predominant Gut Microbiota: A Double-Blind, Placebo-Controlled Trial.

Bifidobacteria are important intestinal bacteria that provide a variety of health benefits in infants. We investigated the efficacy and safety of Bifidobacterium longum subsp. infantis (B. infantis) M-63 in healthy infants in a double-blind, randomized, placebo-controlled trial. Healthy term infants were given B. infantis M-63 (n = 56; 1 × 109 CFU/day) or placebo (n = 54) from postnatal age ≤ 7 days to 3 months. Fecal samples were collected, and fecal microbiota, stool pH, short-chain fatty acids, and immune substances were analyzed. Supplementation with B. infantis M-63 significantly increased the relative abundance of Bifidobacterium compared with the placebo group, with a positive correlation with the frequency of breastfeeding. Supplementation with B. infantis M-63 led to decreased stool pH and increased levels of acetic acid and IgA in the stool at 1 month of age compared with the placebo group. There was a decreased frequency of defecation and watery stools in the probiotic group. No adverse events related to test foods were observed. These results indicate that early supplementation with B. infantis M-63 is well tolerated and contributes to the development of Bifidobacterium-predominant gut microbiota during a critical developmental phase in term infants.

External Jugular Venous Aneurysm: A Case Report.

Venous aneurysms of the external jugular vein (EJV) are exceedingly rare. During the 21-year period from 2000 to 2020, only 30 cases were reported. There have been no reports of serious complications associated with EJV aneurysms. Treatment is mainly for cosmetic reasons, but sometimes for pain or other symptoms. Currently, surgical excision is the most commonly applied therapeutic strategy. In this report, we present the case of a 40-year-old previously healthy woman who presented with a painful mass in her left supraclavicular area after a mild left neck contusion injury one month earlier. A venous aneurysm of the left EJV was diagnosed on the basis of vascular ultrasound and computed tomography angiography and venography findings. The patient underwent surgical removal of the EJV aneurysm for the symptom of pain. The EJV was repaired and preserved based on the intraoperative findings. The treatment resulted in cosmetic improvement and pain relief, with no signs of recurrence.

Serological Screening of Immunoglobulin G against SARS-CoV-2 Nucleocapsid and Spike Protein before and after Two Vaccine Doses among Healthcare Workers in Japan.

This study sought to evaluate the effects of two vaccine doses and the extent of SARS-CoV-2 infection among healthcare workers. We measured immunoglobulin G antibody titers against SARS-CoV-2 nucleocapsid and spike protein among healthcare workers at Gunma University Hospital. In March 2021, prior to BNT-162b2 vaccination, two of 771 participants were seropositive for nucleocapsid and spike protein, whereas 768 were seronegative. The remaining one participant was seropositive for nucleocapsid protein but seronegative for spike protein. A total of 769 participants were seropositive for spike protein after two vaccination doses. The two seropositive participants prior to vaccination showed the highest antibody titers after the second vaccination. They were probably infected with SARS-CoV-2 without clinical symptoms before March 2021. Four weeks after the second vaccination, a younger age was associated with higher antibody titers against SARS-CoV-2 spike protein. Thirty-two weeks after the second vaccination, blood samples were collected from 342 of 769 participants. Antibody titers at 32 weeks after the second vaccination significantly decreased compared with those at 4 weeks after the second vaccination among all age groups. The rate of decrease in antibody titers between 4 and 32 weeks after the second vaccination was greater in the female participants. No sex differences were observed in the antibody titers within each age group. BNT-162b2 vaccination thus induced seroconversion in an age-dependent manner. Serological screening could further establish the likelihood of subclinical SARS-CoV-2 infection.

[Rupture of Coronary Artery Aneurysm with Coronary Artery to Pulmonary Artery Fistula;Report of a Case].

We report a rare case of ruptured coronary artery aneurysm. A 58-year-old woman experienced a sudden chest pain. Coronary arteriography( CAG) and computed tomography(CT) showed pericardial effusion and 2 saccular coronary artery aneurysms connected by a communicating artery. The 1st one was originated from the right coronary artery and flowed to the communicating artery. The 2nd one was originated from both the diagonal branch and the communicating artery, and flowed to the main pulmonary artery, forming a fistula. Since the 1st one was larger, it was suspected to be the rupture site. Emergency operation was performed and the aneurysms were directly closed under cardiopulmonary bypass. The postoperative course was uneventful.

Thenar Dysplasia in Radial Polydactyly Depends on the Level of Bifurcation.

BACKGROUND: Little is known about thenar dysplasia in radial polydactyly, other than that thenar hypoplasia occasionally occurs in radial polydactyly with triphalangism. In particular, the phenotype and level of duplication associated with thenar dysplasia remain unclear. METHODS: The abductor pollicis brevis and flexor pollicis brevis muscles were visualized using three-dimensional ultrasound, and their horizontal geometry was assessed using a biaxial level classification system. Subjects were categorized into three phenotypes according to the developmental condition of the radial thumb. The relationship between the level of distribution of the muscles and the level of the bifurcation of the radial thumb was investigated. RESULTS: Nineteen patients with radial polydactyly without triphalangism were included. There were 10 patients with the nonfloating type, three with the floating type, and six with the rudimentary type. All patients with bifurcation at or more distal to the metacarpophalangeal joint had normal thenar muscle distribution, but the muscles in patients with bifurcation at or more proximal to the level of the metacarpals were confined, regardless of phenotype. The level of muscle distribution was strongly correlated with the level of the bifurcation of the radial thumb. CONCLUSIONS: These findings suggest that formation of the thenar muscles in the longitudinal direction in radial polydactyly might depend on the level of bifurcation of the radial thumb. The presence of thenar dysplasia even in floating-type or rudimentary-type duplications is of clinical and etiologic importance.

The effect of tolvaptan on renal excretion of electrolytes and urea nitrogen in patients undergoing coronary artery bypass surgery.

BACKGROUND: Adequate fluid management is an important component of patient care following cardiac surgery. Our aim in this study was to determine the benefits of tolvaptan, an oral selective vasopressin-2 receptor antagonist that causes electrolyte-free water diuresis, in postoperative fluid management. We prospectively examined the effect of tolvaptan on renal excretion of electrolytes and urea nitrogen in cardiac surgery patients. METHODS: Patients undergoing coronary artery bypass surgery were randomized to receive conventional loop diuretics (Group C, n = 30) or conventional loop diuretic therapy plus tolvaptan (Group T, n = 27). Fractional excretions of sodium (FENA), potassium (FEK) and urea nitrogen (FEUN) were measured in both groups during post-surgical hospitalization. RESULTS: Urine output was greater with tolvaptan (Group T) than without it (Group C), and some patients in Group C required intravenous as well as oral loop diuretics. Serum sodium concentrations decreased after surgery in Group C, but were unchanged in Group T (postoperative day [POD] 3, 139.8 ± 3.5 vs. 142.3 ± 2.6 mEq/L, p = 0.006). However, postoperative FENA values in Group C did not decrease, and the values were similar in both groups. Serum potassium levels remained lower and FEK values remained higher than the preoperative values, but only in Group C (all p < 0.05). BUN increased postoperatively in both groups, but it remained higher than its preoperative value only in Group C (all p < 0.01). Group T showed an initial increase in BUN, which peaked and then returned to its preoperative value within a week. The FEUN increased postoperatively in both groups, but the change was more pronounced in Group T (POD7, 52.7 ± 9.3 vs. 58.2 ± 6.5 %, p = 0.025). CONCLUSIONS: Renal excretion of sodium and potassium reflects the changes in serum concentration in patients treated with tolvaptan. Patients treated only with loop diuretics showed a continuous excretion of sodium and potassium that led to electrolyte imbalance, whereas the combination of loop diuretics and tolvaptan increased renal urea nitrogen elimination. Tolvaptan therefore appears to be an effective diuretic that minimally affects serum electrolytes while adequately promoting the elimination of urea nitrogen from the kidneys in patients undergoing coronary artery bypass surgery. TRIAL REGISTRATION: The present study is registered with the UMIN Clinical Trials Registry (ID: UMIN000011039 ).

A Case of Extensive Sacral Decubitus Ulcer Complicated by an Epidural Abscess.

We herein report a 62-year-old man with an extensive sacral decubitus ulcer complicated by an epidural abscess. An epidural abscess is a rare disease, but it should be considered in the differential diagnosis of a deep infection with decubitus. Moreover, the diagnosis may be late in such instances and should be carefully considered when a patient has paralysis.

Preoperative hepatic dysfunction could predict postoperative mortality and morbidity in patients undergoing cardiac surgery: Utilization of the MELD scoring system.

BACKGROUND: According to recent advances in operative techniques, an increasing number of patients with liver dysfunction have been subjected to cardiac surgery. Model of End-Stage Liver Disease (MELD and MELD-XI) scores allow risk stratification of patients undergoing cardiac and non-cardiac surgeries. METHODS: We retrospectively analyzed 1856 consecutive patients (69.3% male, mean 66.8 ± 12.2 years) undergoing cardiac surgery between 2008 and 2013 at our institution. RESULTS: The mean values of MELD/MELD-XI scores obtained from the total cohort were 9.7 ± 4.6/11.9 ± 4.8. Patients with high MELD/MELD-XI scores (>12) were older, more anemic, and had lower left ventricular ejection fraction than those with low scores (all p<0.0001). High scores were associated with longer hospitalization (36.8 ± 33.0 vs. 23.6 ± 21.5 days for MELD, 36.7 ± 34.0 vs. 23.5 ± 21.0 days for MELD-XI, both p<0.0001) and higher in-hospital all-cause mortality (6.6% vs. 1.0% for MELD, 7.7% vs. 0.7% for MELD-XI). Atrial fibrillation occurred more frequently in the high MELD group, but this difference was not found for MELD-XI. MELD/MELD-XI could predict mortality with a sensitivity of 64.3%/60.0% and specificity of 79.1%/85.3%. Comparison of AUC values among MELD scores, individual MELD components, and Child-Turcotte-Pugh (CTP) classification showed that the predictive strength of MELD scores for mortality was stronger than individual parameters or CTP classification (AUC: 0.7702 for MELD, 0.7655 for MELD-XI, 0.5799 for CTP classification with pairwise p<0.0001 and p=0.0002 vs. MELD and MELD-XI, respectively). CONCLUSIONS: Assessment of liver dysfunction using the MELD scores can be useful for predicting postoperative morbidity and mortality, which may allow additional risk stratification in patients undergoing cardiac surgery.

A stable human progesterone receptor expressing HeLa reporter cell line as a tool in chemical evaluation at the different cell-cycle phases.

Specific molecular events, characteristic of each cell-cycle phase may have direct effect to the functionality of nuclear receptors. Based on this understanding, the evaluation of lipophilic chemicals at the different cell-cycle phases is significant and should be considered. In order to achieve the aim of performing large-scale dose-response analysis on the effects of lipophilic chemicals at the different cell-cycle phases, a stable, sensitive and highly selective human progesterone receptor (hPR) expressing HeLa reporter cell line, hPRLuc-20, was established. Upon the establishment of the hPRLuc-20 cells, they were synchronized to the G(1), S and G(2) phases and treated with progesterone (PROG) and promegestone (R5020). The cells successfully showed that at the different cell-cycle phase, both agonists resulted in different cellular responses. The differences in response supports that hPR expressed within the hPRLuc-20 cells do respond in a cell-cycle dependent manner, thus showing the cells' compatibility in large-scale dose-response analyses of chemicals. It is hopeful that the advanced application of the hPRLuc-20 cells could contribute to provide fundamental hints to further understand the function of hPR, and provide key observations to elucidate the nature of these chemicals with hPR, its corresponding co-regulators and transcription factors.

Elimination of abnormal sialylglycoproteins in fibroblasts with sialidosis and galactosialidosis by normal gene transfer and enzyme replacement.

Sialidosis and galactosialidosis are lysosomal storage diseases caused by the genetic defects of lysosomal sialidase (neuraminidase-1; NEU1) and lysosomal protective protein/cathepsin A (PPCA), respectively, associated with a NEU1 deficiency, excessive accumulation of sialylglycoconjugates, and development of progressive neurosomatic manifestations; in addition, the latter disorder is accompanied by simultaneous deficiencies of beta-galactosidase and cathepsin A. We demonstrated that a few soluble N-glycosylated proteins carrying sialyloligosaccharides sensitive to glycopeptidase F (GPF) can be specifically detected in cultured fibroblasts from sialidosis and galactosialidosis cases by blotting with a Maackia amurensis (MAM) lectin. We also examined the therapeutic effects of normal gene transfer and enzyme replacement by evaluating the decreases in sialylglycoconjugates accumulated in fibroblasts with these NEU1 deficiencies. The specific N-glycosylated proteins detected on MAM lectin blotting as well as the granular lysosomal fluorescence due to an avidin-FITC/biotinylated MAM lectin conjugate in sialidosis and galactosialidosis fibroblasts disappeared in parallel with the restoration of the intracellular NEU1 activity after transfection of the recombinant NEU1 fused to HA tag sequence and the wild-type PPCA cDNA as well as administration of the recombinant PPCA precursor protein. The detection method for the abnormal sialylglycoproteins in cultured cells involving MAM lectin was demonstrated to be useful not only for biochemical and diagnostic analyses of NEU1 deficiencies but also for therapeutic evaluation of these conditions.