Prognostic impact of aberrant right hepatic artery involvement in patients with pancreatic cancer: A multicenter retrospective cohort study.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the prognostic value of aberrant right hepatic artery (A-RHA) involvement in patients with pancreatic cancer (PC). METHODS: This study enrolled 474 patients who underwent upfront pancreatectomy or neoadjuvant treatment for resectable (R) or borderline resectable (BR) PC from four institutions. The patients were divided into three groups: A-RHA involvement group (n = 12), patients who had sole A-RHA involvement without major arterial involvement; BR-A group (n = 104), patients who had major arterial involvement; R/BR-PV group (n = 358), others. RESULTS: All patients in the A-RHA involvement group underwent margin-negative resection. The median overall survival of the entire cohort in the A-RHA involvement, R/BR-PV, and BR-A groups was 41.2, 33.5, and 25.2 months, respectively. Although survival in the R/BR-PV group was significantly more favorable than that in the BR-A group (p = 0.0003), no significant difference was observed between the A-RHA involvement group and the R/BR-PV (p = 0.7332) and BR-A (p = 0.1485) groups. CONCLUSIONS: The prognosis of patients with PC and sole A-RHA involvement was comparable to that of patients with R/BR-PV.

Novel multifunctional plant growth-promoting bacteria isolated from the oil palm rhizosphere under long-term organic matter application.

Most agricultural products are presently cultivated on marginal lands with poor soil properties and unfavorable environmental conditions (diseases and abiotic stresses), which can threaten plant growth and yield. Plant growth-promoting bacteria (PGPB) are beneficial bacteria that promote plant growth and biomass and act as biocontrols against diseases and stress. However, most isolated PGPBs have a single function and low survival rates owing to their limited growth behaviors. In this study, we isolated multifunctional PGPB from oil palm rhizosphere, quantitatively measured their activities, and evaluated their effectiveness in Brassica rapa (Komatsuna) cultivation. This is the first study to report the isolation of three multifunctional PGPB strains with ammonium production, phosphate-potassium-silicate solubilization, and indole-3-acetic acid (IAA) production from the oil palm rhizosphere, namely Kosakonia oryzendophytica AJLB38, Enterobacter quasimori AJTS77, and Lelliottia jeotgali AJTS83. Additionally, these strains showed antifungal activity against the oil palm pathogen Ganoderma boninense. These strains grow under high temperature, acidic and alkaline pH, and high salt concentration, which would result in their proliferation in various environmental conditions. The cultivation experiments revealed these strains improved the growth and biomass with half the dosage of chemical fertilizer application, which was not significantly different to the full dosage. Furthermore, the overall plant growth-promoting activities in quantitative assays and overall B. rapa growth in cultivation experiments were statistically correlated, which could contribute to the prediction of plant growth promotion without plant cultivation experiments. Thus, the selected PGPB could be valuable as a biofertilizer to improve soil health and quality and promote agricultural sustainability.

Isolated hair bacteria reveal different isolation possibilities under various conditions.

Microorganisms are assumed to inhabit various environments and organisms, including the human body. The presence of more than 700 bacterial species on scalp hair has been reported through rRNA gene amplicon analysis. However, the biological properties of bacteria on the scalp hair (hair bacteria) and their functions are poorly understood as few hair bacteria have been isolated from hair in previous studies. This study aimed to isolate hair bacteria using standard media under 24 different conditions (including medium components, component concentrations, gelling agents, and atmospheric environments). Furthermore, we evaluated the possibility of isolating strains under these isolation conditions and examined the carbon metabolic ability of several predominantly isolated strains. A total of 63 bacterial species belonging to 27 genera were isolated from hair under 24 isolation conditions. The predominant bacterial species isolated from human hair in this study showed different carbon metabolic capabilities than those of the reference strains. In addition, isolation possibility was newly proposed to systematically evaluate the number of isolation conditions that could cultivate a bacterial species. Based on isolation possibility, the isolates were categorized into groups with a high number of isolation conditions (e.g., ≥25%; such as Staphylococcus) and those with a low number (e.g., ≤25%; such as Brachybacterium). These findings indicate the existence of easily isolated microorganisms and difficultly isolated microorganism from human hair.

Distal gastrectomy and Roux-en-Y reconstruction for refractory reflux esophagitis after proximal gastrectomy and esophagogastric anastomosis reconstruction.

Refractory gastroesophageal reflux disease can develop after proximal gastrectomy and esophagogastrostomy. We introduce a new method that combines distal gastrectomy and Roux-en-Y reconstruction to treat refractory reflux esophagitis in patients who have undergone proximal gastrectomy and esophagogastric anastomosis reconstruction. This novel method may be useful not only for alleviating the symptoms of gastroesophageal reflux disease but also for preventing future esophageal malignancies arising from long-term reflux esophagitis.

Effects of Resistance Exercise and Essential Amino Acid Intake on Muscle Quality, Myokine, and Inflammation Factors in Young Adult Males.

BACKGROUND: Recently, many studies have been devoted to discovering nutrients for exercise-like effects. Resistance exercise and the intake of essential amino acids (EAAs) are known to be factors that can affect muscle mass and strength improvement. The purpose of this study was to investigate changes in muscle quality, myokines, and inflammation in response to resistance exercise and EAA supplementation. METHODS: Thirty-four males volunteered to participate in this study. They were assigned to four groups: (1) placebo (CO), (2) resistance exercise (RE), (3) EAA supplementation, and (4) RE + EAA supplementation. Body composition, muscle quality, myokines, and inflammation were measured at baseline and four weeks after treatment. RESULTS: Lean body fat had decreased in both RE and RE + EAA groups. Lean body mass had increased in only the RE + EAA group. In all groups except for CO, irisin, myostatin A, and TNF-α levels had decreased. The grip strength of the right hand and trunk flexion peak torque increased in the RE group. The grip strength of the left hand, trunk flexion peak torque, and knee flexion peak torque of the left leg were increased in RE + EAA. CONCLUSIONS: RE, EAA, and RE + EAA could effectively improve the muscle quality, myokine, and inflammation factors of young adult males. This finding highlights the importance of resistance exercise and amino acid intake.

A multicenter retrospective observational NAPOLEON2 study of nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable pancreatic cancer.

Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38-85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64-1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings.

[Neuropathology of Disorders Leading to Dementia].

Dementia is characterized by acquired cognitive dysfunction caused by various neurological disorders. Many neurological conditions can cause dementia, including neurodegenerative diseases, vascular disorders, infections, inflammation, demyelination, intoxication, metabolic disorders, tumors, and head trauma. Despite recent developments in biomarkers and imaging techniques, neuropathological examination is necessary for the final diagnosis. Moreover, approximately 11% of the patients with dementia have dual or triple pathological conditions. The coexistence of neurological diseases makes it difficult for neurologists to diagnose patients accurately. Degenerative diseases are characterized by neuronal loss with gliosis in distinct parts of the brain, the presence of neuronal or glial inclusions, and abnormal protein accumulation. Senile plaques and neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease. These findings are characterized by the presence of amyloid ß protein (Aß) and phosphorylated tau protein, respectively. Although vascular dementia is common, it may be difficult to identify the relationship between vascular lesions and cognitive impairment. The incidence of sporadic Aß-type cerebral amyloid angiopathy (CAA) tends to increase with age and causes dementia due to vascular dysfunction and leukoencephalopathy. Furthermore, patients with CAA can develop inflammation. Clinical neurologists should possess a neuropathological perspective for the appropriate diagnosis and management of patients with dementia.

Different traits for cold tolerance of extremely thermophilic Calditerricola strains isolated from mesothermal municipal sewage sludge and its hyperthermal compost.

Extreme thermophiles Calditerricola satsumensis DD2 and D3 were isolated from mesothermal municipal sludge, a material used for hyperthermal composting. To understand the ecologically anomalous findings, their behavior at various temperatures, membrane fatty acid composition, and draft genome sequences were compared with those of C. satsumensis YMO81T and Calditerricola yamamurae YMO722T, already isolated from hyperthermal compost. All four strains grew between 56 and 83 °C. However, strains DD2 and D3 were stable for ≥48 h at a wide range of temperatures (20-75 °C), while strains YMO81T and YMO722T were highly labile at lower temperatures. The former strains maintained their colony-forming ability for >180 days at 20 °C, while the latter strains lost it within 1 d. All four strains showed similar composition of membrane fatty acid, which were not affected by 20 °C treatment. Comparative draft genome analyses showed that 13 candidate genes were present only in strains DD2 and D3, and the specific expression of six gene homologs was confirmed. A DNA chaperone, site-specific recombinase XerD homolog, had tetra adenine sequence at its upper gene region, and was up-regulated by 20 °C treatment in DD2 and D3, suggesting a possible role in the cold tolerance of sludge-derived strains. In addition, the lack of another possible DNA chaperone, a homolog of the ATP-dependent DNA helicase, in the compost-derived strains may accelerate their sensitivity to cold shock. In conclusion, we speculate that the specific phenotypic and genotypic characteristics of sludge-derived strains are responsible for their unusual ecological distribution at ambient temperatures.

Thrombotic microangiopathy in a patient with anti-signal recognition particle antibody-positive immune-mediated necrotizing myopathy.

We describe the case of a 61-year-old woman with anti-signal recognition particle (SRP) antibody-positive immune-mediated necrotizing myopathy (IMNM) who exhibited biopsy-confirmed thrombotic microangiopathy (TMA). The patient developed proximal-dominant muscle weakness and was diagnosed with anti-SRP antibody-positive IMNM based on muscle biopsy results and serological examination. A high-dose corticosteroid prescription was initiated, followed by intravenous methylprednisolone and intravenous immunoglobulin therapy (IVIg). The patient showed IVIg-induced hemolytic anemia with preserved ADAMTS13 activity. Transient oral tacrolimus administration was initiated. Approximately 8 weeks after admission, the serum creatinine levels gradually increased. Renal histological examination revealed TMA, including ischemic changes in the renal tubules, stenosis, and occlusion of the interlobular arteries with fibrinoid necrosis of the afferent arteriolar walls. The arteriolar walls demonstrated an accumulation of C1q and C3c. Myofiber damage in patients with IMNM accounts for the activation of the classical pathway of the complement cascade in the sarcolemma due to antibody deposition. Additionally, a membrane attack complex is observed on capillaries in the muscle tissues of patients with anti-SRP antibody-positive IMNM. Although drug-induced pathomechanisms, such as IVIg and tacrolimus, can trigger the development of TMA, we suggest that the presence of serum anti-SRP antibodies would be implicated in complement-associated kidney vascular damage.

Influence of Percutaneous Transhepatic Gallbladder Aspiration and Drainage for Severe Acute Cholecystitis on the Surgical Outcomes of Subsequent Laparoscopic Cholecystectomy: Post Hoc Analysis of the CSGO-HBP-017 (CSGO-HBP-017C).

OBJECTIVE: Percutaneous transhepatic gallbladder aspiration (PTGBA) and/or drainage (PTGBD) are useful approaches in the management of acute cholecystitis in patients who cannot tolerate surgery because of poor general condition or severe inflammation. However, reports regarding its effect on the surgical outcomes of subsequent laparoscopic cholecystectomy (LC) are sparse. The aim of this retrospective study was to investigate the influence of PTGBA on surgical outcomes of subsequent LC by comparing the only-PTGBA group, including patients who did not need the additional-PTGBD, versus the additional-PTGBD group, including those who needed the additional-PTGBD after PTGBA. PATIENTS AND METHODS: We conducted a post hoc analysis of our multi-institutional data. This study included 63 patients who underwent LC after PTGBA, and we compared the surgical outcomes between the only-PTGBA group (n = 56) and the additional-PTGBD group (n = 7). RESULTS: No postoperative complications occurred among the 63 patients, and the postoperative hospital stay was 11 ± 12 days. Fourteen patients (22.2%) had a recurrence of cholecystitis, of whom 7 patients (11.1%) needed the additional-PTGBD after PTGBA. Significantly longer operative time (245 ± 74 vs 159 ± 65 min, P = 0.0017) and postoperative hospital stay (22 ± 27 vs 10 ± 9 d, P = 0.0118) and greater intraoperative blood loss (279 ± 385 vs 70 ± 208 mL, P = 0.0283) were observed among patients in the additional-PTGBD group compared with the only-PTGBA group, whereas the rates of postoperative complications (Clavien-Dindo grade ≥3: 0% each) and conversion to open surgery (28.6% vs 8.9%, P = 0.1705) were comparable. CONCLUSION: PTGBA for acute cholecystitis could result in good surgical outcomes of subsequent LC, especially regarding postoperative complications. However, we should keep in mind that the additional-PTGBD after PTGBA failure, which sometimes happened, would be associated with increased operative difficulty and longer recovery.

Scalp bacterial species influence SIRT1 and TERT expression in keratinocytes.

Scalp bacteria on the human scalp and scalp hair comprise distinct community structures for sites and individuals. To evaluate their effect on human keratinocyte cellular activity, including that of the hair follicular keratinocytes, the expression of several longevity genes was examined using HaCaT cells. A screening system that uses enhanced green fluorescent protein (EGFP) fluorescence was established to identify scalp bacteria that enhance silent mating type information regulation 2 homolog-1 (SIRT1) promoter activity in transformed HaCaT cells (SIRT1p-EGFP). The results of quantitative polymerase chain reaction revealed that several predominant scalp bacteria enhanced (Cutibacterium acnes and Pseudomonas lini) and repressed (Staphylococcus epidermidis) the expressions of SIRT1 and telomerase reverse transcriptase (TERT) genes in HaCaT cells. These results suggest that the predominant scalp bacteria are related to the health of the scalp and hair, including repair of the damaged scalp and hair growth, by regulating gene expression in keratinocytes.

Distribution of bacterial community structures on human scalp hair shaft in relation to scalp sites.

Bacterial community structure on the human skin is specific to each individual and varies among different body sites. In this study, we investigated differences in bacterial community structure among 5 hair sampling sites and among 12 individuals. Significant differences were found between individuals in terms of alpha diversity and relative abundance of major bacterial phyla and genera, whereas no differences were found between hair sampling sites. The principal coordinate analysis plots of within-individual group tended to converge individually, whereas those of within-hair sampling site group did not cluster. In addition, weighted UniFrac analysis showed that the individual-based category was a statistically significant category but not the scalp hair sampling site-based category. These results suggest that the distribution of bacterial community structures on scalp hair shafts within individuals was relatively steady, even when the scalp hair sampling site was different.

Dilution rates and their transition modes influence organic acid productivity and bacterial community structure on continuous meta-fermentation using complex microorganisms.

We investigated the effect of dilution rates (D) (0.05, 0.15, and 0.4 h-1) and its transition mode strategies (constant, up, and down modes) on organic acid productivity and bacterial community structure on continuous meta-fermentation using complex microorganisms. The number of bacterial species decreased with increasing D in the constant mode while up and down modes maintained high and low values, respectively, regardless of the changing D values. Caldibacillus hisashii was the predominant species in all modes at all D values, while other bacterial species, including Anaerosalibacter bizertensis and Clostridium cochlearium were predominant in only certain modes and D values. The highest total organic acid productivity of 3.16 g L-1 h-1 was obtained with 82.2% lactic acid selectivity at D = 0.4 h⁻1 in constant mode. Heterofermentation occurred in the up mode, while the down mode exhibited the maximum butyric acid productivity of 0.348 g L-1 h-1 with 43.8% selectivity at D = 0.05 h-1. The constant, up, and down modes showed the distinct main products of lactic, acetic and formic, and butyric acids, respectively. In this study, we proposed a new parameter of species-specific productivity (SSP) to estimate which species and how much a bacterium quantitatively contributes to the targeted organic acid productivity in continuous meta-fermentation. SSP was determined based on the abundance of functional genes encoding key enzymes from the results of 16S amplicon analysis. In conclusion, D values and their transition modes affect productivity by changing the bacterial community structure, and are a significant factor in establishing a highly productive process in continuous meta-fermentation.

[A Case of Sister Mary Joseph's Nodule after Radiation Therapy for Cervical Cancer].

An umbilical metastasis from an internal malignancy is called Sister Mary Joseph's nodule(SMJN)and has a poor prognosis. Herein, we report a case of umbilical metastasis of cervical cancer. A woman in her eighties underwent radiation therapy for cervical cancer(cT3bN0M0, cStage ⅢB). Primary tumor shrank after treatment, suggesting that radiation therapy induced complete response. Two years and 9 months after treatment, the patient presented with umbilical pain. A CT scan showed an umbilical mass near the umbilical hernia. PET-CT demonstrated high accumulation of FDG at the mass, which led to suspicion of umbilical metastasis(SMJN). Although she underwent radical surgery, she died from cancer 8 months after surgery.

Vacuoles related to tissue neuron-astrocyte ratio and infiltration of macrophages/monocytes contribute to hyperintense brain signals on diffusion-weighted magnetic resonance imaging in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Radiological features in patients with sporadic Creutzfeldt-Jakob disease (sCJD) are hyperintensity of the cerebral cortex and the basal ganglia displayed by diffusion-weighted magnetic resonance imaging (DW-MRI). We performed a quantitative study on neuropathological and radiological findings. METHODS: Patient 1 received a definite diagnosis of MM1-type sCJD, while patient 2 received a definite diagnosis of MM1 + 2-type sCJD. Two DW-MRI scans were performed on each patient. DW-MRI was either taken the day before or on the day of the patient's death, and several hyperintense or isointense areas were marked as a region of interest (ROI). Mean signal intensity of the ROI was measured. Pathological quantitative assessments of the vacuoles, astrocytosis, infiltration of monocytes/macrophages, and proliferation of microglia was performed. Vacuole load (% area vacuole), glial fibrillary acidic protein (GFAP), CD68, and Iba-1 load were calculated. We defined spongiform change index (SCI) to indicate vacuoles related to a tissue neuron-astrocyte ratio. We assessed the correlation of intensity of the last DW-MRI and the pathological findings as well as association of changes of the signal intensity on the sequential images and the pathological findings. RESULT: We observed a strong positive correlation between SCI and DW-MRI intensity. In the analysis using serial DW-MRI and pathological findings, we found that CD68 load was significantly larger in areas where signal intensity decreased, as compared to those areas where hyperintensity remained unchanged. CONCLUSION: DW-MRI intensity in sCJD is associated with the ratio of neuron to astrocyte in the vacuoles and the infiltration of macrophages and/or monocytes.

[A Case of Thoracic Esophageal Cancer Treated with COVID-19 Pneumonia during Preoperative Chemoradiotherapy(CRT)].

INTRODUCTION: There is concerned that prognosis of cancer-bearing patients is adversely affected by postponement of cancer treatment due to infection with a new type of coronavirus(COVID-19). We report a case of thoracic esophageal cancer treated with COVID-19 pneumonia during preoperative CRT. A 60-year-old female diagnosed as having Stage Ⅳ thoracic esophageal cancer(cT3N0M1LYM[104R])started receiving preoperative chemoradiotherapy. On the 12th day, she had a fever and was diagnosed with COVID-19 infection. CRT temporarily interrupted and she was treated for COVID-19 pneumonia preferentially. CRT was resumed promptly after remission. Finally, video-Assisted radical esophagectomy was performed. There were no postoperative complications. Nivolumab was started as an adjuvant therapy on the 2nd postoperative months. CONCLUSIONS: We experienced a case of thoracic esophageal cancer in which COVID-19 pneumonia was treated during preoperative CRT, and CRT and surgery were completed without complications by appropriate treatment.

[A Case of Conversion Surgery after Long-Term Chemotherapy for Pancreatic Cancer with Peritoneal Metastasis].

A 66-year-old woman was referred to the gastroenterology division of our hospital due to elevation of serum CEA level. Contrast-enhanced CT showed a hypovascular tumor at the body of pancreas. She was diagnosed with pancreatic cancer by EUS-FNA. By laparotomy, we found white nodules on mesentery and abdominal wall, which were diagnosed as peritoneal metastasis. After systemic chemotherapy with 9 courses of gemcitabine(GEM)plus nab-paclitaxel(PTX)and 30 courses of mFOLFIRINOX, the tumor had shrunk and serum CA19-9 level were remarkably decreased. Distal pancreatectomy was performed as conversion surgery. Pathological analysis revealed no remnant cancer cells in the primary tumor or the lymph nodes, confirming a pCR. S-1 was started as adjuvant chemotherapy, and she remains alive without recurrence 8 months after surgery.

[A Case of Hepatocellular Carcinoma Extending into Right Atrium Was Resected Successfully Using Cardiopulmonary Bypass].

A 59-year-old male was referred to our hospital for a thorough examination of liver function abnormality in the background of chronic hepatitis C. Abdominal contrast-enhanced CT showed multiple tumors in the right lobe of the liver, and an 8 cm tumor occupying S7, a tumor thrombus extending from the right hepatic vein to the inferior vena cava, and a tumor thrombus in the right branch of the portal vein. The patient was diagnosed with hepatocellular carcinoma, cT4N0M0, cStage ⅣA. After 5 courses of hepatic arterial infusion therapy, the intrahepatic lesion was significantly reduced, but micropulmonary metastasis appeared, and the tumor thrombus in the inferior vena cava increased to the thoracic inferior vena cava and just below the tricuspid valve. The patient had difficulty blocking blood flow in the inferior vena cava in the pericardial sac. The patient underwent right hepatectomy, tumor thrombus resection of the inferior vena cava, combined resection of the inferior vena cava, and bovine pericardial patch reconstruction under artificial cardiopulmonary support. He was discharged on the 23rd day after surgery and has been under outpatient observation for 16 months while receiving molecular-targeted drugs for lung metastasis.

Cerebrospinal Fluid Biomarkers and Amyloid-ß Elimination from the Brain in Cerebral Amyloid Angiopathy-Related Inflammation.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) have demonstrated inconsistent results. OBJECTIVE: We investigated the relationship between CSF amyloid-ß protein (Aß) and vascular pathological findings to elucidate the mechanisms of Aß elimination from the brain in CAA-ri. METHODS: We examined Aß40 and Aß42 levels in CSF samples in 15 patients with CAA-ri and 15 patients with Alzheimer's disease and cerebral amyloid angiopathy (AD-CAA) using ELISA as a cross-sectional study. Furthermore, we pathologically examined Aß40 and Aß42 depositions on the leptomeningeal blood vessels (arteries, arterioles, and veins) using brain biopsy samples from six patients with acute CAA-ri and brain tissues of two autopsied patients with CAA-ri. RESULTS: The median Aß40 and Aß42 levels in the CSF showed no significant difference between pre-treatment CAA-ri (Aß40, 6837 pg/ml; Aß42, 324 pg/ml) and AD-CAA (Aß40, 7669 pg/ml, p = 0.345; Aß42, 355 pg/ml, p = 0.760). Aß40 and Aß42 levels in patients with post-treatment CAA-ri (Aß40, 1770 pg/ml, p = 0.056; Aß42, 167 pg/ml, p = 0.006) were lower than those in patients with pre-treatment CAA-ri. Regarding Aß40 and Aß42 positive arteries, acute CAA-ri cases showed a higher frequency of partially Aß-deposited blood vessels than postmortem CAA-ri cases (Aß40, 20.8% versus 3.9%, p = 0.0714; Aß42, 27.4% versus 2.0%, p = 0.0714, respectively). CONCLUSION: Lower levels of CSF Aß40 and Aß42 could be biomarkers for the cessation of inflammation in CAA-ri reflecting the recovery of the intramural periarterial drainage pathway and vascular function.

Effects of Melissa officinalis Extract Containing Rosmarinic Acid on Cognition in Older Adults Without Dementia: A Randomized Controlled Trial.

BACKGROUND: Previous in vitro and in vivo studies on Alzheimer's disease (AD) models have reported that rosmarinic acid (RA) can inhibit the formation of amyloid-ß fibrils as well as the oligomerization and deposition of amyloid-ß protein. Melissa officinalis (M. officinalis) extract containing 500 mg of RA is tolerable and safe in healthy individuals and patients with mild AD dementia. OBJECTIVE: This randomized placebo-controlled double-blind trial aimed to assess the effects of M. officinalis extract on cognition in older adults without dementia. METHODS: This study included individuals who were diagnosed with subjective or mild cognitive impairment (n = 323). The trial involved M. officinalis extract supplementation (500 mg of RA per day) period of 96 weeks followed by a washout period of 24 weeks. The primary endpoint was the Alzheimer's Disease Assessment Scale-cognitive subscale score, and the secondary endpoints were other cognitive measure results as well as safety and tolerability. RESULTS: There were no significant differences in cognitive measures between the placebo and M. officinalis groups from baseline to 96 weeks. However, based on the analysis of Clinical Dementia Rating Sum of Boxes scores in participants without hypertension, the score was found to be increased by 0.006 and decreased by 0.085 in the M. officinalis and placebo groups, respectively; this difference was statistically significant (p = 0.036). Furthermore, there were no differences in vital signs, physical and neurological measures, or hippocampal volume between the two groups. CONCLUSION: These results indicate that M. officinalis extract may help prevent cognitive decline in older adults without hypertension.