Cognitive Digital Biomarkers from Automated Transcription of Spoken Language.

BACKGROUND: Although patients with Alzheimer's disease and other cognitive-related neurodegenerative disorders may benefit from early detection, development of a reliable diagnostic test has remained elusive. The penetration of digital voice-recording technologies and multiple cognitive processes deployed when constructing spoken responses might offer an opportunity to predict cognitive status. OBJECTIVE: To determine whether cognitive status might be predicted from voice recordings of neuropsychological testing. DESIGN: Comparison of acoustic and (para)linguistic variables from low-quality automated transcriptions of neuropsychological testing (n = 200) versus variables from high-quality manual transcriptions (n = 127). We trained a logistic regression classifier to predict cognitive status, which was tested against actual diagnoses. SETTING: Observational cohort study. PARTICIPANTS: 146 participants in the Framingham Heart Study. MEASUREMENTS: Acoustic and either paralinguistic variables (e.g., speaking time) from automated transcriptions or linguistic variables (e.g., phrase complexity) from manual transcriptions. RESULTS: Models based on demographic features alone were not robust (area under the receiver-operator characteristic curve [AUROC] 0.60). Addition of clinical and standard acoustic features boosted the AUROC to 0.81. Additional inclusion of transcription-related features yielded an AUROC of 0.90. CONCLUSIONS: The use of voice-based digital biomarkers derived from automated processing methods, combined with standard patient screening, might constitute a scalable way to enable early detection of dementia.

Outcomes of robot-assisted versus conventional laparoscopic low anterior resection in patients with rectal cancer: propensity-matched analysis of the National Clinical Database in Japan.

BACKGROUND: Robot-assisted laparoscopic surgery has several advantages over conventional laparoscopy. However, population-based comparative studies for low anterior resection are limited. This article aimed to compare peri-operative results of robot-assisted low anterior resection (RALAR) and laparoscopy. METHODS: This retrospective cohort study used data from patients treated with RALAR or conventional laparoscopic low anterior resection (CLLAR) between October 2018 and December 2019, as recorded in the Japanese National Clinical Database, a data set registering clinical information, perioperative outcomes, and mortality. Of note, the registry does not include information on the tumour location (centimetres from the anal verge) and diverting stoma creation. Perioperative outcomes, including rate of conversion to open surgery, were compared between RALAR and CLLAR groups. Confounding factors were adjusted for using propensity score matching. RESULTS: Of 21 415 patients treated during the study interval, 20 220 were reviewed. Two homogeneous groups of 2843 patients were created by propensity score matching. The conversion rate to open surgery was significantly lower in the RALAR group than in the CLLAR group (0.7 versus 2.0 per cent; P < 0.001). The RALAR group had a longer operating time (median: 352 versus 283 min; P < 0.001), less intraoperative blood loss (15 versus 20 ml; P < 0.001), a lower in-hospital mortality rate (0.1 versus 0.5 per cent; P = 0.007), and a shorter postoperative hospital stay (median: 13 versus 14 days; P < 0.001) compared with the CLLAR group. The CLLAR group had a lower rate of readmission within 30 days (2.4 versus 3.3 per cent; P = 0.045). CONCLUSION: These data highlight the reduced conversion rate, in-hospital mortality rate, intraoperative blood loss, and length of postoperative hospital stay for rectal cancer surgery in patients treated using robot-assisted laparoscopic surgery compared with laparoscopic low anterior resection.

Disease-modifying effects of COX-2 selective inhibitors and non-selective NSAIDs in osteoarthritis: a systematic review.

Osteoarthritis (OA) is a potentially disabling disease whose progression is dependent on several risk factors. OA management usually involves the use of non-steroidal anti-inflammatory drugs (NSAIDs) that are the primary pharmacological treatments of choice. However, NSAIDs have often been associated with unwanted side effects. Cyclooxygenase (COX)-2 specific inhibitors, such as celecoxib, have been successfully used as an alternative in the past for OA treatment and have demonstrated fewer side effects. While abundant data are available for the clinical efficacy of drugs used for OA treatment, little is known about the disease-modifying effects of these agents. A previous review published by Zweers et al. (2010) assessed the available literature between 1990 and 2010 on the disease-modifying effects of celecoxib. In the present review, we aimed to update the existing evidence and identify evolving concepts relating to the disease-modifying effects of not just celecoxib, but also other NSAIDs. We conducted a review of the literature published from 2010 to 2016 dealing with the effects, especially disease-modifying effects, of NSAIDs on cartilage, synovium, and bone in OA patients. Our results show that celecoxib was the most commonly used drug in papers that presented data on disease-modifying effects of NSAIDs. Further, these effects appeared to be mediated through the regulation of prostaglandins, cytokines, and direct changes to tissues. Additional studies should be carried out to assess the disease-modifying properties of NSAIDs in greater detail.

The long-term outcome of transvaginal anterior levatorplasty for intractable rectovaginal fistula.

AIM: Several procedures have been described for rectovaginal fistula with a wide range of success, but there is little information on the long-term outcome. The aim of the present study was to investigate the long-term outcome after transvaginal anterior levatorplasty (ALP) for intractable rectovaginal fistula. METHOD: Data of 16 consecutive patients undergoing transvaginal ALP with fistulectomy and closure of the rectum and vagina between 1998 and 2011 were prospectively recorded and retrospectively investigated to study the long-term outcome. RESULTS: Birth injury (n = 7), low anterior resection for rectal cancer (n = 3), pouch surgery for ulcerative colitis (n = 2) and a procedure for prolapse and haemorrhoids (n = 2) were the main causes of the fistula. Nine patients had a covering stoma before surgery. All patients underwent ALP, with a covering stoma in two patients. Infection occurred in one patient and wound rupture after surgery in another patient. These patients underwent reoperation by ALP. All fistulae had healed at a median follow-up of 84 (8-193) months after initial surgery or stoma closure. CONCLUSION: Transvaginal ALP is effective for the treatment of mid or low rectovaginal fistula. The results show that a graft is not necessary regardless of whether or not previous surgery has been performed.

Short-term outcomes of local correction of stoma prolapse with a stapler device.

BACKGROUND: The aim of the present study was to classify the short-term outcomes of local correction of stoma prolapse with a stapler device. METHODS: The medical records of 11 patients undergoing local correction of stoma prolapse using a stapler device were retrospectively reviewed. RESULTS: No mortality or morbidity was observed after the surgery. Median operative time was 35 min (range 15-75 min), and blood loss was minimal. Median duration of follow-up was 12 months (range 6-55 months). One of the 11 patients had a recurrent stoma prolapse. CONCLUSIONS: This technique can be a feasible, safe and minimally invasive correction procedure for stoma prolapse.

Simple excision and closure of a distal limb of loop colostomy prolapse by stapler device.

Stomal prolapse is one of the common complications in transverse colostomy and can be managed conservatively in most cases; however, laparotomy and reconstruction of the stoma may sometimes be required, especially in case of irreducible colostomy prolapse. We have reported a simple local repair with reconstruction of the loop colostomy. We herein report a new more simple technique to avoid laparotomy and allow excision of the irreducible colostomy prolapse and complete closure of the distal limb of loop colostomy when no decompression is required in the distal limb of the stoma. In this procedure, the number of stapler and the time with blood loss for the operation can be saved.

Effect of edaravone on ischemia/reperfusion injury in rat urinary bladder--changes in smooth muscle cell phenotype and contractile function.

Edaravone is a newly developed radical scavenging agent that has been widely used for protection against ischemia/reperfusion (I/R) injury in patients with cerebral infarction. The present study investigated the effects of edaravone on the I/R injury in rat urinary bladder. Adult male rats were divided in the four groups: groups 1-3 received 1 hour of ischemia followed by 1 hour of reperfusion with saline and with edaravone (1 and 3 mg/kg body weight), and group 4 were age-matched control rats. The in vivo ischemia was created by clamping the vesical arteries for 1 hour and reperfusion was accomplished by removing the clips and lasted for 1 hour. Edaravone or saline were administered after reperfusion for 30 min. Following reperfusion, the bladder was excised and separated. Bladder smooth muscle cell (SMC) phenotypic expression was investigated in the electron microscope. The number of contractile and non-contractile bladder SMC phenotype according to the morphological criteria was counted and the ratio of non-contractile to contractile phenotype was calculated. The responses to electrical field stimulation and carbachol were recorded. Edaravone administration resulted in the protection of the morphological changes and contractile responses to both EFS and carbachol that were affected by the agent. Our findings demonstrate that edaravone has a potentially protective effect on I/R-induced damage in the rat bladder.

Hyperactive mutants of mouse D-aspartate oxidase: mutagenesis of the active site residue serine 308.

The role of Ser-308 of murine D-aspartate oxidase (mDASPO), particularly its side chain hydroxyl group, was investigated through the use of site-specific mutational analysis of Ser-308. Recombinant mDASPO carrying a substitution of Gly, Ala, or Tyr for Ser-308 was generated, and fused to either His (His-mDASPO), or glutathione S-transferase, His, and S (GHS-mDASPO) at its N-terminus. Wild-type His-mDASPO or GHS-mDASPO or their mutant derivatives were expressed in Escherichia coli and purified by affinity chromatography. All purified recombinant proteins had functional DASPO activity. The Gly-308 and Ala-308 mutants had significantly higher catalytic efficiency towards D-Asp and N-methyl-D-Asp, and a higher affinity for flavin adenine dinucleotide (FAD) compared to the wild-type enzyme. The Tyr-308 mutant had lower catalytic efficiency and binding capacity. These results suggest that the side chain hydroxyl group of a critical residue of mDASPO, Ser-308, down-regulates enzymatic activity, substrate binding, and FAD binding. This study provides information on the active site of DASPO that will considerably enhance our understanding of the biological significance of this enzyme.

Engineered synthetic pathway for isopropanol production in Escherichia coli.

A synthetic pathway was engineered in Escherichia coli to produce isopropanol by expressing various combinations of genes from Clostridium acetobutylicum ATCC 824, E. coli K-12 MG1655, Clostridium beijerinckii NRRL B593, and Thermoanaerobacter brockii HTD4. The strain with the combination of C. acetobutylicum thl (acetyl-coenzyme A [CoA] acetyltransferase), E. coli atoAD (acetoacetyl-CoA transferase), C. acetobutylicum adc (acetoacetate decarboxylase), and C. beijerinckii adh (secondary alcohol dehydrogenase) achieved the highest titer. This strain produced 81.6 mM isopropanol in shake flasks with a yield of 43.5% (mol/mol) in the production phase. To our knowledge, this work is the first to produce isopropanol in E. coli, and the titer exceeded that from the native producers.

Multi-layered network structure of amino acid (AA) metabolism characterized by each essential AA-deficient condition.

The concentrations of free amino acids in plasma change coordinately and their profiles show distinctive features in various physiological conditions; however, their behavior can not always be explained by the conventional flow-based metabolic pathway network. In this study, we have revealed the interrelatedness of the plasma amino acids and inferred their network structure with threshold-test analysis and multilevel-digraph analysis methods using the plasma samples of rats which are fed diet deficient in single essential amino acid. In the inferred network, we could draw some interesting interrelations between plasma amino acids as follows: 1) Lysine is located at the top control level and has effects on almost all of the other plasma amino acids. 2) Threonine plays a role in a hub in the network, which has direct links to the most number of other amino acids. 3) Threonine and methionine are interrelated to each other and form a loop structure.

Creatol, an oxidative product of creatinine in kidney transplant patients, as a useful determinant of renal function: a preliminary study.

Creatol (CTL, 5-hydroxycreatinine) is a creatinine (Cr) oxidative metabolite, which was originally isolated from the urine of patients with chronic renal failure, representing a candidate for a uremic toxin. The effectiveness of CTL as an indicator of oxidative stress after kidney transplantation has not been reported. Therefore, we examined the relation between the change in oxidative stress (using CTL) in renal transplant patients and their change in renal function (using Cr). The serum Cr and serum and urine CTL were examined in five renal transplant patients. Serum CTL closely correlated with serum Cr. Serum CTL also correlated with urine CTL, but in some cases there was a time lag. Both the ratio of CTL/(Cr) and serum CTL observed in patient 2 were slow to improve after transplantation. The process through which oxidative stress was reduced was shown by the index of renal damage correlated with kidney function oxidative stress (using serum CTL) after transplantation. Our data suggested that CTL/Cr may be a good indicator of graft prognosis.

Can monitoring of serum 8-OHdG level for 2 hours after renal transplantation predict prognosis of the graft?

8-Hydroxy-2'-deoxyguanosine (8-OHdG) is an oxidant of deoxyguanosine, a base in the construction of DNA. We examined the extent of DNA damage to the graft through oxidative stress after renal transplantation. Seven renal transplant patients were enrolled in this study. Before reperfusion of the grafts, the level of serum 8-OHdG was measured using enzyme-linked immunosorbent assay. No relationship was found between the level of serum 8-OHdG just before reperfusion and the postoperative course. In all cases, the level of serum 8-OHdG increased after reperfusion and decreased within 2 hours. In six cases, it remained almost the same as the preoperative level. A faster rate of decrease from the first peak of serum 8-OHdG was associated with a lower nadir serum creatinine and reduced occurrence of acute rejection. This study suggested that immediate calming of the oxidative stress following reperfusion may potentially have a positive influence on graft prognosis. In addition, biomarkers of oxidative stress may predict graft prognosis.

Enterocele associated with rectocele revealed by dynamic pelvic CT.

Enterocele is often associated with other pelvic floor disorders but it is not always possible to detect by clinical examination. Defecography with peritoneography and/or barium meal intake has recently been developed as a new method to identify enterocele, but this method is an invasive procedure. Multislice computed tomography was performed at rest and during simulated defecation to evaluate an 80-year-old female patient who had a defecation disorder and was diagnosed as having rectocele based on results from defecography and clinical findings. Multiplanar reconstruction images were generated for image evaluation. Using this novel method of dynamic pelvic computed tomography, a third-degree enterocele was clearly demonstrated in this case.

A new technique of laparoscopic surgery for rectal disease.

Laparoscopic rectal surgery is a technique that has to be done in a narrow space: the pelvis. If an immoderate operation is performed with a difficult view, for example in female where the field is disturbed by uterus, it is possible to produce organ trauma or an unexpected bleeding. Taking these problems in mind, we performed laparoscopic surgery in 44 cases of rectal disease with several techniques which we have invented. In these cases either the uterus or the rectum was retracted in the narrow space, and if an anterior resection was to be done, the tape was tied tightly around the rectum below the tumor to avoid touching the tumor and leaving adequate vascular irrigation to the remnant rectum. With the use of our techniques, we did not have female intestinal injury or unexpected bleeding. In addition laparoscopic anterior resection of rectum did not cause any intestinal injury, or unexpected bleeding or anastomotic leakage; also we did not have any local tumor recurrence. It is our belief that these techniques can decrease complications that traumatize the grasping intestine with intestinal forceps and prevent implantation in the anastomosis. This technical report validate that our technique modifications for rectal laparoscopic surgery are useful when a surgeon has to work in a narrow space.

Transvaginal anterior levatorplasty with posterior colporrhaphy for symptomatic rectocele.

BACKGROUND: We evaluated functional and morphological outcomes of transvaginal anterior levatorplasty with posterior colporrhaphy for symptomatic rectocele. METHODS: Ten women (median 68 years) underwent transvaginal anterior levatorplasty with posterior colporrhaphy for symptomatic rectocele. Symptoms and continence were monitored before and after surgery. Manovolumetric study and defecography were performed in 9 of 10 patients before and 3-6 months after surgery. Twenty-one females without anorectal diseases were used as controls in manovolumetric study. The patients were followed up after a median of 89 months (range, 3-103). RESULTS: Main symptoms (defecatory disorders in 9 patients, vaginal mass in 6, perineal discomfort in 2) disappeared after surgery. Six patients performed digitation preoperatively and gave up digitation on defecation after surgery. Stool incontinence disappeared in 4 of 5 preoperatively incontinent patients (Cleveland clinic score, 5-12) and continence score improved from 5 to 2 in the remaining patient. Three patients with urinary cough incontinence preoperatively did not experience incontinence after surgery but cough incontinence occurred occasionally in an 81-year-old patient postoperatively. Rectocele demonstrated on defecography disappeared postoperatively in all 9 patients who underwent defecography. High threshold volume and maximum tolerable volume, which were observed preoperatively, decreased to control levels after surgery. CONCLUSION: Transvaginal anterior levatorplasty with posterior colporrhaphy might be an option for symptomatic rectocele to improve anorectal and urinary dysfunctions with morphological disorders.

Quantitative structure-retention relationships of phenolic compounds without Hammett's equations.

Retention times of phenolic compounds in a given pH eluent in reversed-phase liquid chromatography were predicted from dissociation constants derived from atomic partial charges and log P-values calculated by a computational chemical method. The precision of the calculation of atomic partial charges by AMI and PM3 methods of MOPAC was evaluated. The atomic partial charges obtained by AMI were the more acceptable. The atomic partial charges obtained from the hydrogen of the hydroxyl group included an ortho-effect, therefore an ortho-effect was added to the predicted values. The precision of predicted retention factors obtained using predicted pKa values was similar to that using reference pKa values.

Postrenal acute renal failure during pregnancy 20 years after antireflux surgery.

We report that a 27-year-old woman with bilateral severe hydronephorosis during pregnancy 20 years after antireflux surgery. The patient developed postrenal acute renal failure due to obstruction of the lower ureter. This patient could safely give birth after bilateral percutaneous nephrostomy through joint management with the obstetrics and gynecology staff. We describe that stenosis of the lower ureter is a late complication of antireflux surgery.