Scar Outcome in Unilateral Complete Cleft Lip Repair: A Comparative Analysis of Vertical Lip Lengthening Strategies Using the Rotation-Advancement Concept.

OBJECTIVE: To assess the differences in scar outcomes between modified rotation-advancement techniques proposed by Drs. Mohler and Noordhoff, designed to address issues such as inadequate vertical lip length and scarring on the upper third of the lip in the original rotation-advancement technique. DESIGN: Retrospective single-surgeon (RD) study. PATIENTS: Consecutive non-syndromic children (n = 68) with unilateral complete cleft lip and palate. INTERVENTIONS: Modified Mohler (columellar backcut reconstructed with C flap; n = 34) and modified Noordhoff (lower, medially-created backcut reconstructed with laterally-based triangular skin flap; n = 34) repairs. MEAN OUTCOME MEASURES: Using 12-month postoperative frontal photographs, scar evaluations (overall and superior, middle, and inferior portions of the lip) were appraised by an assessment panel composed by independent professional and nonprofessional raters employing four validated qualitative scar assessment scales: Manchester Scar Scale, modified Scar-Rating Scale, Stony Brook Scar Evaluation Scale, and Visual Analog Scale. Quantitative computerized photogrammetric scar widths of the superior, middle, and inferior portions of the upper lip were also measured. RESULTS: The modified Noordhoff method showed significantly (all P < .001) better scar quality for the overall scar and superior portion of the scar in all four scales compared to the modified Mohler method, with no significant (all P > .05) difference for the middle and lower portions. No significant difference (all P > .05) was observed for photogrammetric scar width measurements. CONCLUSION: The modified Noordhoff technique provided better qualitative results for unilateral complete cleft lip-related scars compared to the modified Mohler technique.

Prognostic impact of oral anticoagulation therapy and atrial fibrillation in patients with type B acute aortic dissection.

Background: The prognostic impact of atrial fibrillation (AF) and oral anticoagulation (OAC) therapy in patients with type B acute aortic dissection (AAD) remains unclear. Therefore, we investigated the prognostic impact of AF and OAC therapy in patients with type B AAD. Methods: Consecutive patients diagnosed with AAD were included in this single-center, retrospective study. Patients with type B AAD were selected from the study population and divided into three groups: AF(+)/OAC(+), AF(+)/OAC(-), and AF(-)/OAC(-). The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, progressive aortic events, cerebral infarction, and organ malperfusion. Results: In total, 139 patients diagnosed with type B AAD were analyzed. AF was observed in 27 patients (19%). Among them, 13 patients (9%) received OAC therapy for AF. MACCE occurred in 32 patients (23%) during the observation period: all-cause death in four patients, progressive aortic events in 24 patients, cerebral infarction events in two patients, and malperfusion events in two patients. The incidence of MACCE was higher in the AF(+)/OAC(+) group than in the AF(+)/OAC(-) group (hazard ratio[HR]: 3.875; 95% confidence interval [CI]: 1.153-17.496). In contrast, there was no significant difference in the incidence of MACCE between the AF(+)/OAC(-) and AF(-)/OAC(-) groups (HR: 1.001, 95% CI: 0.509-1.802). Conclusion: Among patients with type B AAD, the use of OAC for AF was associated with a higher risk of MACCE.

Validating the Modified Small Double Opposing Z-Plasty for Palatal Lengthening in Primary Palatoplasty.

OBJECTIVE: To appraise the degree of intraoperative palatal lengthening with the modified Furlow small double-opposing Z-plasty (sDOZ). DESIGN: Retrospective single-surgeon (R.D.) study. PATIENTS: Nonsyndromic children (n = 167) with Veau types I to IV cleft palates who underwent primary sDOZ palatoplasty. INTERVENTIONS: Intraoperative measurements of palatal lengths and widths were collected using calipers, paper rulers, and metal rulers before the administration of local anesthetic solution and before the removal of the mouth gag (initial and final palatal dimensions, respectively). MAIN OUTCOME MEASURES: Assessment of the intraoperative percentage change (difference between final and initial values) in surface palatal length, straight palatal length, and soft palatal length. Bivariate and multivariate analyses were performed to identify independent predictors (sex, age at surgery, Veau, Kernahan/ Stark, and Randall classifications, widest cleft width, presence of lateral relaxing incision, type of coverage with buccal fat flap, and postoperative complications) of soft palatal lengthening. RESULTS: Surface palatal, straight palatal, and soft palatal lengths had an intraoperative increase of 8%, 14.7%, and 27.7%, respectively. The degree of intraoperative soft palatal lengthening significantly varied among Veau cleft types (I = II < III = IV). Veau type III and cleft lip/palate were independent positive predictors (P < .001) of soft palatal lengthening, while other tested variables were not correlated (P > .05) with this outcome. CONCLUSIONS: Overall intraoperative palatal lengthening occurs with the modified sDOZ palatoplasty, with differences within the spectrum of cleft palate deformity.

Prolonged hiccups induced by renal infarction: a case report.

BACKGROUND: Hiccups are common symptoms that last for less than 48 hours. However, we encountered a case of renal infarction in a patient with prolonged hiccup. The relationship between hiccups and renal infarction is important in differentiating patients with prolonged hiccups. CASE PRESENTATION: An 87-year-old Japanese man with atrial fibrillation and receiving antithrombotic therapy presented to the emergency department with prolonged hiccups. The patient discontinued antithrombotic therapy for atrial fibrillation due to subcortical bleeding, after which he experienced right back pain. He was diagnosed with right renal infarction based on computed tomography images, and the antithrombotic therapy was continued. The patient's hiccups ceased, and he was discharged on hospital day 11. CONCLUSION: Hiccups can be induced by various clinical conditions. It is hypothesized that the inflammation of the right kidney infarction stimulated the diaphragm and induced prolonged hiccups in this patient; this theory is supported by the computed tomography images. This case report shows that internal organ diseases irritating the diaphragm can cause hiccups, and renal disease should be considered in patients with prolonged hiccups.

Single-Splint, 2-Jaw Orthognathic Surgery for Correction of Facial Asymmetry: 3-Dimensional Planning and Surgical Execution.

Three-dimensional (3D) planning of orthognathic surgery (OGS) improves the treatment of facial asymmetry and malocclusion, but no consensus exists among clinicians regarding technical details. This study verified the consistency of authors' workflow and strategies between 3D planning and surgical execution for facial asymmetry. This retrospective study recruited consecutive patients (n=54) with nonsyndromic facial asymmetry associated with malocclusion. The stepwise workflow included orthodontic treatment, 3D imaging-based evaluation, planning, and transferring the virtual of single-splint 2-jaw OGS to actual surgery in all patients. Seven landmark-based measurements were selected for postoperative assessment of facial symmetry. Fifty patients had no anesthetic/surgical-related episode and procedure-related complications. Others experienced wound infection (n=1), transient TMJ discomfort (n=1), and facial numbness (n=3). Two cases had minor residual asymmetry (cheek and chin, respectively), but did not request revisionary bone or soft tissue surgery. Comparisons between the planned and postoperative 3D images with quantitative measurement revealed acceptable outcome data. The results showed a significant increase in facial symmetry at 7 landmark-based postoperative measurements for both male and female. This 3D-assisted pathway of OGS permitted achievement of consistent satisfactory results in managing facial asymmetry, with low rate of complications and secondary management.

Impact of increased reimbursement for ambulance transportation on hospital acceptance in Japan: a difference-in-difference study.

OBJECTIVE: Emergency medical services (EMS) often face difficulties in finding accepting hospitals in Japan. The universal medical insurance system in Japan increased the reimbursement for ambulance transportation acceptance at night, and on Sundays and holidays from 1 April 2016. This study investigated the effect of the reimbursement increase on the number of EMS calls, and transportation time from arrival at the scene to arrival at the hospital. DESIGN: A difference-in-difference study. The treatment group consisted of people who called an ambulance at night while the control group consisted of people who called an ambulance during the daytime. SETTING: The national ambulance records of the Fire and Disaster Management Agency in Japan from 1 April 2015 to 31 December 2016. PARTICIPANTS: 7 625 463 ambulance dispatches were eligible for inclusion. PRIMARY AND SECONDARY OUTCOME MEASURES: The changes in EMS calls, transportation time and the number of ambulance transports per 1000 population in one month in a comparison of daytime and night-time transport. RESULTS: The treatment effect (night-time vs daytime) on the number of EMS calls was -0.013 (95% CI, -0.023 to -0.004), which was significant. The transportation time decreased slightly by 0.080 min (95% CI, -0.157 to -0.004). No impact was observed on the number of ambulance transports per 1000 population per month (0.00; 95% CI, -0.008 to 0.002). CONCLUSION: An increase in reimbursement for ambulance transportation acceptance was associated with a decrease in the number of EMS calls. Further strategies for decreasing the number of EMS calls are needed to avoid delays in the treatment of emergency patients with critical illness.

Analysis of the NUDT15 gene and metabolites of azathioprine in Japanese patients with inflammatory bowel disease.

BACKGROUND: Thiopurines continue to play an important role in the treatment of inflammatory bowel disease (IBD). It is well known that thiopurines can cause several adverse reactions. Especially, hematopoietic toxicity may lead to severe agranulocytosis. In a previous prospective study, we investigated the relationship between inosine triphosphate pyrophosphatase (ITPA) c.94c > a polymorphism, 6-thioguanine nucleotide (6-TGN) concentration and toxicity. METHODS: To clarify the cause of thiopurine toxicity, we analysed nucleoside disphosphate-linked moiety X-type motif 15 (NUDT15) gene polymorphisms, i.e., R139C, V18I, and V19_V19insGV, and measured 6-mercaptopurines and 6-methylmercaptopurines (6-MMP) using the archived blood samples collected from 49 IBD patients for our previous study. RESULTS: The ITPA c.94c > a polymorphism was detected in 19 patients (38.7%, all heterozygous). The R139C polymorphism was found in 10 patients (20.4%, 1 homozygous, 9 heterozygous), V18_V19insGV in 7 patients (14.3%, all heterozygous), and V18I in 2 patients (4.08%, all heterozygous). Although R139C was more strongly associated with leukopenia than c.94c > a, there were no significant correlations with 6-TGN and 6-MMP levels, as for c.94c > a. The leukopenia incidence rates for each gene polymorphism were 0% in those with all wild-type genes, 21.4% for c.94c > a only, 42.9% for NUDT15 polymorphism (s) only, and 80.0% for both polymorphisms. CONCLUSIONS: All cases of leukopenia were associated with ITPA c.94c > a and/or polymorphism of NUDT15 and the risk of developing leukopenia was synergistically increased by ITPA and NUDT15 gene polymorphism. However, there was no association between the level of azathioprine metabolites and these polymorphisms.

Long-Term Outcome of Primary Rhinoplasty with Overcorrection in Patients with Unilateral Cleft Lip: Avoiding Intermediate Rhinoplasty.

BACKGROUND: No consensus exists regarding the timing or technique of rhinoplasty for correction of the unilateral cleft lip nose deformity, with few studies examining the long-term effects of a single technique. This study appraised the long-term outcomes of primary rhinoplasty using the Tajima technique for overcorrection in a cohort of patients with unilateral cleft lip nose deformity after attaining skeletal maturity. METHODS: Consecutive nonsyndromic patients with unilateral cleft lip nose deformity ( n = 103) who underwent primary rhinoplasty with overcorrection by a single surgeon between 2000 and 2005 were reviewed. Patients with unilateral cleft lip and nasal deformity who underwent primary rhinoplasty (but with no overcorrection) ( n = 30) and noncleft individuals ( n = 27) were recruited for comparison. Outcomes were assessed through FACE-Q scales evaluating satisfaction with appearance of nose and nostrils (two scales) and computer-based objective photogrammetric analysis of nasal symmetry (nostril height, nostril width, nostril area, alar height, and alar width parameters). RESULTS: Significant differences (all P < 0.001) were observed between the Tajima and non-Tajima groups for all but one photogrammetric nasal parameter (nostril area), with the Tajima group demonstrating closer mean values to the noncleft group. The Tajima and noncleft groups demonstrated no significant difference (all P > 0.05) for scores of FACE-Q nose and nostrils scales. CONCLUSION: This study indicated that the patients who underwent primary rhinoplasty with overcorrection had improved results with no necessity for intermediate rhinoplasty, emphasizing that the procedure is an effective approach to correct the unilateral cleft nose deformity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Impact of Bifidobacterium adolescentis in patients with abdominal aortic aneurysm: a cross-sectional study.

The relationships between various diseases and the human gut microbiota (GM) have been revealed. However, the relationships between the human abdominal aortic aneurysm (AAA) and GM remains unknown. The aim of this cross-sectional study was to clarify the association between the human AAA and GM. Stool samples from 30 consecutive patients with AAA before aneurysm repair and those of 30 controls without vascular diseases were analyzed by 16S rRNA gene (V3-4) sequencing using an Illumina MiSeq system and QIIME 2. There was no significant difference in age (75 vs. 75 years) or gender (80% vs. 87% males) between the groups. No significant difference in GM composition was observed in principal coordinate analysis between the two groups, whereas the AAA group showed a significantly lower abundance of Bifidobacterium adolescentis (p<0.01) at the species level than the controls. This study demonstrated that the abundance of B. adolescentis decreased in patients with AAA. This is the first study to show the characteristics of the GM in patients with AAA. Studies are needed to reveal if causal relationships exists between the human AAA and GM.

Usefulness of Bifidobacterium longum BB536 in Elderly Individuals With Chronic Constipation: A Randomized Controlled Trial.

INTRODUCTION: Few reports exist regarding the therapeutic effects of probiotics on chronic constipation in elderly individuals. This study evaluated the effects of Bifidobacterium longum BB536 in elderly individuals with chronic constipation. METHODS: This was a randomized, double-blind placebo-controlled, parallel-group superiority trial in Japan (UMIN 000033031). Eighty older adults diagnosed with chronic constipation were randomly assigned (1:1) to receive either probiotics ( B. longum BB536, 5 × 10 10 colony-forming unit, n = 39) or placebo (n = 41) once daily for up to 4 weeks. The severity of constipation was evaluated using the Constipation Scoring System. The primary end point was the difference in the changes from baseline in the constipation scoring system total score between the 2 groups at week 4. RESULTS: A total of 79 patients (mean age of 77.9 years), including 38 patients in the BB536 group and 41 in the placebo group, completed the study. The primary end point was not significant ( P = 0.074), although there was significant improvement ( P < 0.01) in the BB536 group from baseline to week 4, but there were no significant changes in the placebo group. There was a significant difference and a tendency toward a difference in the changes from baseline on the stool frequency ( P = 0.008) and failure of evacuation ( P = 0.051) subscales, respectively, at week 4 between the 2 groups. Few adverse events related to the probiotics were observed. DISCUSSION: The primary end points were not significant. However, probiotic supplementation significantly improved bowel movements. These results suggest that B. longum BB536 supplementation is safe and partially effective for improving chronic constipation in elderly individuals.

Dysbiosis of the Fecal and Biliary Microbiota in Biliary Tract Cancer.

Characteristic bile duct and gut microbiota have been identified in patients with chronic biliary tract disease. This study aimed to characterize the fecal and bile microbiota in biliary tract cancer (BTC) patients and their relationship. Patients with BTC (n = 30) and benign biliary disease (BBD) without cholangitis (n = 11) were included. Ten healthy, age-matched subjects were also recruited for fecal microbiota comparison. The fecal and bile duct microbiotas were analyzed by sequencing the 16S rRNA gene V3-V4 region. Live bacteria were obtained in the bile from three BTC patients by culture, and metagenomics-based identification was performed. Linear discriminant analysis effect size showed a higher Enterobacteriaceae abundance and a lower Clostridia abundance, including that of Faecalibacterium and Coprococcus, in the BTC patients than in the other subjects. Ten of 17 operational taxonomic units (OTUs) assigned to Enterobacteriaceae in the bile were matched with the OTUs found in the BTC subject fecal samples. Furthermore, a bile-isolated strain possessed the carcinogenic bacterial colipolyketide synthase-encoding gene. Enterobacteriaceae was enriched in the BTC feces, and more than half of Enterobacteriaceae in the bile matched that in the feces at the OTU level. Our data suggests that fecal microbiota dysbiosis may contribute to BTC onset.

Modified Medial Incision Small Double-Opposing Z-Plasty for Treating Veau Type I Cleft Palate: Is the Early Result Reproducible?

OBJECTIVE: An inspiring early result with no oronasal fistula formation was recently described for a modified medial incision small double-opposing Z-plasty (MIsDOZ) for treating Veau type I cleft palate. This study describes an early single-surgeon experience in applying this newly proposed surgical approach. DESIGN: Retrospective single-surgeon study. PATIENTS: Consecutive nonsyndromic patients (n = 27) with Veau I cleft palate. INTERVENTIONS: Topographic anatomical-guided MIsDOZ palatoplasty with pyramidal space dissection (releasing of the ligamentous fibers in the greater palatine neurovascular bundle and pyramidal process region, in-fracture of the pterygoid hamulus, and widening of space of Ernst) performed by a novice surgeon (RD). MEAN OUTCOME MEASURES: Age at surgery, the presence of cleft lip, palatal cleft width, use of lateral relaxing incision, and 6-month complication rate (bleeding, dehiscence, fistula, and flap necrosis). A published senior surgeon-based outcome dataset (n = 24) was retrieved for comparison purposes. RESULTS: Twenty-two (81.5%) and 5 (18.5%) patients received the medial incision only technique and lateral incision technique, respectively (P = .002). Age, presence of cleft lip, and cleft width were not associated (all P > .05) with the use of lateral incision. Comparative analysis between the novice surgeon- and senior surgeon-based datasets revealed no significant differences for sex (females: 74.1% vs 62.5%; P = .546), age (10.2 ± 1.7 vs 9.6 ± 1.2 months; P = .143), rate of lateral incision (18.5% vs 4.2%; P = .195), and postoperative complication rate (0% vs 0%). CONCLUSION: This modified DOZ palatoplasty proved to be a reproducible procedure for Veau I cleft palate closure, with reduced need for lateral incision and with no early complication.

Endovascular thrombectomy using a stent retriever catheter for massive pulmonary thromboembolism.

Acute massive pulmonary thromboembolism (PE) has a high mortality rate of 18%-65%. Along with anticoagulation and thrombolytic therapy, treatment may require a catheter-based thrombectomy or surgical thrombectomy. We report a case of pulmonary thromboembolism treated with a Stent Retriever (Trevo® NXT ProVue Retriever, Stryker, Kalamazoo, MI, USA), which is commonly used to treat stroke. An 81-year-old woman complained of back pain and was transported to our hospital after she became unconscious. Cardiopulmonary resuscitation was initiated before her arrival at the hospital; she returned to spontaneous circulation after arrival. After undergoing computed tomography (CT) scanning, she went into cardiac arrest again, and we established veno-arterial extracorporeal membrane oxygenation and performed catheter thrombectomy using a stent retriever. The left basilar pulmonary artery and the right middle pulmonary artery trunk were retrieved after the stent's deployment, and bilateral pulmonary arteries were confirmed to be reopened. A residual thrombus was present, and Monteplase was administered. A contrast-enhanced CT scan taken on day 15 following admission revealed that the thrombus had disappeared, and echocardiography revealed improved right ventricular dysfunction. The patient was transferred to another hospital on day 64 for rehabilitation. We report the first case of pulmonary artery thrombosis that was successfully recanalized by endovascular treatment with a stent retriever. The stent retriever may be useful as an endovascular treatment device for PE because it is easier to achieve recanalization using this method compared to conventional treatment methods.

Growth of various obligate and facultative anaerobic intestinal bacteria in cell culture medium under aerobic and anaerobic culture conditions.

Eight bacterial strains were used in this study to examine the survival of intestinal bacteria in immune cell cultures under aerobic and anaerobic culture conditions. With the addition of penicillin G and streptomycin, viable Clostridium clostridioforme and Fusobacterium varium cells did not decrease after 6 or 24 hr, even under aerobic conditions. Without antibiotics, eight bacterial strains did not decrease until 4 or 6 hr later, under both aerobic and anaerobic conditions. Escherichia coli numbers increased by more than 10 times under both conditions. In order to examine the effects of live gut bacteria on various immune cells, the viability of bacteria should be checked in cell culture media and under different conditions.

Extracting time series matching a small-angle X-ray scattering profile from trajectories of molecular dynamics simulations.

Solving structural ensembles of flexible biomolecules is a challenging research area. Here, we propose a method to obtain possible structural ensembles of a biomolecule based on small-angle X-ray scattering (SAXS) and molecular dynamics simulations. Our idea is to clip a time series that matches a SAXS profile from a simulation trajectory. To examine its practicability, we applied our idea to a multi-domain protein ER-60 and successfully extracted time series longer than 1 micro second from trajectories of coarse-grained molecular dynamics simulations. In the extracted time series, the domain conformation was distributed continuously and smoothly in a conformational space. Preferred domain conformations were also observed. Diversity among scattering curves calculated from each ER-60 structure was interpreted to reflect an open-close motion of the protein. Although our approach did not provide a unique solution for the structural ensemble of the biomolecule, each extracted time series can be an element of the real behavior of ER-60. Considering its low computational cost, our approach will play a key role to identify biomolecular dynamics by integrating SAXS, simulations, and other experiments.

The stimulatory effect of fusobacteria on dendritic cells under aerobic or anaerobic conditions.

Fusobacteria have been suspected to be pathobionts of colon cancer and inflammatory bowel disease. However, the immunomodulatory properties that affect these inflammatory reactions in dendritic cells (DCs) under anaerobic and aerobic conditions have not yet been characterized. We directly assessed the stimulatory effects of anaerobic commensal bacteria, including fusobacteria, on a human DC line through coculture under aerobic or anaerobic conditions. Under aerobic or anaerobic conditions, stimulation of the DC line with all live commensal bacteria examined, except the probiotic Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus), significantly increased the geometric mean fluorescent intensity (MFI) of marker proteins (HLA-ABC, HLA-DR, CD80, CD86, CD83, or CCR7) on the DC surface. In particular, both Fusobacterium nucleatum (F. nucleatum) and Escherichia coli (E. coli) significantly increased the expression of DC-associated molecules, except for CD83 under both aerobic and anaerobic conditions. The DC line stimulated with Fusobacterium varium (F. varium) significantly increased only CD80, HLA-ABC, and HLA-DR expression under anaerobic conditions. Moreover, differences in the levels of proinflammatory cytokines, such as IL-6, IL-8, and TNF-α, were detected in the DC line stimulated by all live commensal bacteria under either aerobic or anaerobic conditions. Under aerobic conditions, the DC line stimulated with E. coli produced significantly more IL-6, IL-8, and TNF-α than did the cells stimulated with any of the bacteria examined. When E. coli were used to stimulate the DC line under anaerobic conditions, TNF-α was predominantly produced compared to stimulation with any other bacteria. Compared to the DC line stimulated with any other bacteria, the cells stimulated with F. nucleatum showed significantly increased production of IL-6, IL-8 and TNF-α only under anaerobic conditions. In particular, E. coli, F. nucleatum, and F. varium strongly stimulated the DC line, resulting in significantly increased expression of surface molecules associated with DCs and production of inflammatory cytokines.

Very late stent thrombosis lacking findings of the typical causes on optical coherence tomography in a patient with SARS-CoV-2.

A 50-year-old male was admitted to our hospital with sudden-onset chest pain. He was a current smoker with severe obesity and diabetes. He had a history of drug-eluting stent (DES) implantation in the left anterior descending artery (LAD) and had continuously taken clopidogrel. Eight days prior to admission, polymerase chain reaction testing confirmed that he was positive for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Emergent coronary angiography revealed total occlusion of previously implanted DES in LAD. Optical coherence tomography (OCT) images demonstrated the presence of large white thrombus within the well-expanded DES with homogenous neointima. There were no findings of malapposed strut, uncovered strut, intimal disruption, or neoatherosclerosis through the stented segment. Subsequent dilation using a drug-coated balloon successfully restored coronary flow in LAD. We experienced a case of very late stent thrombosis without findings of the typical causes on OCT images nor discontinuation of antiplatelet therapy in a patient with SARS-CoV-2. The present case suggests that SARS-CoV-2 infection may induce stent thrombosis irrespective of the presence of known causes and the status of antiplatelet therapy. Learning objectives: The underlying causes of very late stent thrombosis (VLST) include strut malapposition, neoatherosclerosis, uncovered struts and stent underexpansion in addition to inadequate discontinuation of antiplatelet therapy and/or systemic hyper coagulable state. The present case of VLST lacking those factors suggests the enhanced hyper thrombogenicity irrespective of the presence of known causes and the status of antiplatelet therapy in patients with severe acute respiratory syndrome coronavirus type 2.

Effect of Probiotic Bifidobacterium breve in Improving Cognitive Function and Preventing Brain Atrophy in Older Patients with Suspected Mild Cognitive Impairment: Results of a 24-Week Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Probiotics have been reported to ameliorate cognitive impairment. OBJECTIVE: We investigated the effect of the probiotic strain Bifidobacterium breve MCC1274 (A1) in enhancing cognition and preventing brain atrophy of older patients with mild cognitive impairment (MCI). METHODS: In this RCT, 130 patients aged from 65 to 88 years old with suspected MCI received once daily either probiotic (B. breve MCC1274, 2×1010 CFU) or placebo for 24 weeks. Cognitive functions were assessed by ADAS-Jcog and MMSE tests. Participants underwent MRI to determine brain atrophy changes using Voxel-based Specific Regional Analysis System for Alzheimer's disease (VSRAD). Fecal samples were collected for the analysis of gut microbiota composition. RESULTS: Analysis was performed on 115 participants as the full analysis set (probiotic 55, placebo 60). ADAS-Jcog subscale "orientation" was significantly improved compared to placebo at 24 weeks. MMSE subscales "orientation in time" and "writing" were significantly improved compared to placebo in the lower baseline MMSE (< 25) subgroup at 24 weeks. VSRAD scores worsened in the placebo group; probiotic supplementation tended to suppress the progression, in particular among those subjects with progressed brain atrophy (VOI Z-score ≥1.0). There were no marked changes in the overall composition of the gut microbiota by the probiotic supplementation. CONCLUSION: Improvement of cognitive function was observed on some subscales scores only likely due to the lower sensitiveness of these tests for MCI subjects. Probiotics consumption for 24 weeks suppressed brain atrophy progression, suggesting that B. breve MCC1274 helps prevent cognitive impairment of MCI subjects.

Overall structure of fully assembled cyanobacterial KaiABC circadian clock complex by an integrated experimental-computational approach.

In the cyanobacterial circadian clock system, KaiA, KaiB and KaiC periodically assemble into a large complex. Here we determined the overall structure of their fully assembled complex by integrating experimental and computational approaches. Small-angle X-ray and inverse contrast matching small-angle neutron scatterings coupled with size-exclusion chromatography provided constraints to highlight the spatial arrangements of the N-terminal domains of KaiA, which were not resolved in the previous structural analyses. Computationally built 20 million structural models of the complex were screened out utilizing the constrains and then subjected to molecular dynamics simulations to examine their stabilities. The final model suggests that, despite large fluctuation of the KaiA N-terminal domains, their preferential positionings mask the hydrophobic surface of the KaiA C-terminal domains, hindering additional KaiA-KaiC interactions. Thus, our integrative approach provides a useful tool to resolve large complex structures harboring dynamically fluctuating domains.