Use of Receiver Operating Curve Analysis and Machine Learning With an Independent Dose Calculation System Reduces the Number of Physical Dose Measurements Required for Patient-Specific Quality Assurance.

PURPOSE: Our purpose was to assess the use of machine learning methods and Mobius 3D (M3D) dose calculation software to reduce the number of physical ion chamber (IC) dose measurements required for patient-specific quality assurance during corona virus disease 2019. METHODS AND MATERIALS: In this study, 1464 inversely planned treatments using Pinnacle or Raystation treatment planning software (TPS) were delivered using Elekta Versa HD and Varian Truebeam and Truebeam STx linear accelerators between June 2018 and November 2019. For each plan, an independent dose calculation was performed using M3D, and an absolute dose measurement was taken using a Pinpoint IC inside the Mobius phantom. The point dose differences between the TPS and M3D calculation and between TPS and IC measurements were calculated. Agreement between the TPS and IC was used to define the ground truth plan failure. To reduce the on-site personnel during the pandemic, 2 methods of receiver operating characteristic analysis (n = 1464) and machine learning (n = 603) were used to identify patient plans that would require physical dose measurements. RESULTS: In the receiver operating characteristic analysis, a predelivery M3D difference threshold of 3% identified plans that failed an IC measurement at a 4% threshold with 100% sensitivity and 76.3% specificity. This indicates that fewer than 25% of plans required a physical dose measurement. A threshold of 1% on a machine learning model was able to identify plans that failed an IC measurement at a 3% threshold with 100% sensitivity and 54.3% specificity, leading to fewer than 50% of plans that required a physical dose measurement. CONCLUSIONS: It is possible to identify plans that are more likely to fail IC patient-specific quality assurance measurements before delivery. This possibly allows for a reduction of physical measurements taken, freeing up significant clinical resources and reducing the required amount of on-site personnel while maintaining patient safety.

Biliverdin protects against the deterioration of glucose tolerance in db/db mice.

AIMS/HYPOTHESIS: We have previously shown a negative correlation between serum bilirubin levels and prevalence of type 2 diabetes, suggesting that bilirubin inhibits development of this disease. To confirm this hypothesis, we investigated whether administration of biliverdin, the precursor of bilirubin, protects against the deterioration of glucose tolerance in db/db mice, a rodent model of type 2 diabetes. METHODS: Biliverdin (20 mg/kg daily) was orally administered to 5-week-old db/db mice for 4 weeks. After 4 weeks of treatment, i.p. glucose tolerance and insulin tolerance tests were performed. Insulin content was evaluated by immunostaining and ELISA. Oxidative stress markers (8-hydroxy-2'-deoxyguansosine and dihydroethidium staining) and expression of NADPH oxidase components Pdx1 and Bax were also evaluated in isolated islets. RESULTS: Treatment with biliverdin partially prevented worsening of hyperglycaemia and glucose intolerance in db/db mice. This effect was accompanied by a significant increase in insulin content and Pdx1 expression, and a significant decrease of apoptosis and Bax expression in pancreatic islets from db/db mice. At the same time, levels of oxidative stress markers and NADPH oxidase component production in islets were normalised. Biliverdin had little effect on HOMA of insulin resistance or insulin resistance evaluated by insulin tolerance tests. CONCLUSIONS/INTERPRETATION: Biliverdin may protect against progressive worsening of glucose tolerance in db/db mice, mainly via inhibition of oxidative stress-induced beta cell damage.

Result of neck clipping and coil embolization as a treatment for subarachnoid haemorrhage.

SUMMARY: The report of the International Subarachnoid Aneurysm Trial (ISAT) study showed that coil embolization was superior to neck clipping as a treatment for subarachnoid haemorrhage (SAH) (1). We compared the results of coil embolization and neck clipping in our institute. Generally better outcomes were obtained by endovascular surgery than neck clipping. Symptomatic vasospasm and symptomatic hydrocephalus occurred less frequently in coil embolization than neck clipping. Because not all cases of SAH can be treated by coil embolization due to the width of aneurysmal neck and relation of the aneurysm to parent arteries, we should also be able to perform neck clipping as another modality.

Villoglandular papillary adenocarcinoma of the uterine cervix responding to neoadjuvant chemotherapy with docetaxel and cisplatin: a case report.

Villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix is a rare neoplasm, and its treatment has rarely been reported. We report a patient with VGPA stage IIA responding to neoadjuvant chemotherapy with docetaxel (60 mg/m2 as an intravenous infusion) and cisplatin (70 mg/m2 as an intra-arterial infusion). At 3 weeks after completing one course of this regimen, the tumor size was reduced from 5.3 x 4.0 cm to 2.0 x 2.0 cm (81.1% reduction), revealed by computed tomography. Accordingly, the patient underwent radical hysterectomy, and there have been no signs of recurrence. Thus, the combination of docetaxel and cisplatin is suggested to be useful for neoadjuvant chemotherapy of cervical adenocarcinoma.

Low dose fraction behavior of high sensitivity radiochromic film.

A high sensitivity (HS) model of radiochromic film is receiving increasing use. The film's linear sensitometric response in the range of 0.5-40 Gy would make this film an ideal candidate for complex dosimetry applications that require tissue equivalence. This study investigates the potential use for clinical dosimetry of typical radiotherapy fractions at relatively low doses (0.5-5 Gy). The experiment involved exposing 25 pre-exposed pieces of HS film to five equal fractions of doses from 0.5 to 5 Gy 24 hours apart. The cumulative dose for each film was carefully monitored and optical density measurements were used as the sole determination of film response to dose. The average behavior of the various fractionation schemes was roughly consistent with previous observations of the MD-55 radiochromic film with about twice the overall sensitivity as expected. However, at low doses and low dose increments, unexpected variations beyond a well-documented low dose nonlinearity were observed. These unexpected variations may indicate complex polymer kinetics at low doses. This type of film would require extra care beyond that described in TG-55 for accurate use at low doses or low dose fraction schemes.

Myrsinionosides A-E: megastigmane glycosides from the leaves of Myrsine seguinii Lev.

Eight megastigmane glycosides were isolated from the leaves of Myrsine seguinii collected in Okinawa. Three of them were found to be known compounds, i.e., ampelopsisionoside, alangionoside J, and linarionoside A. The structures of the new megastigmane glycosides were elucidated from the spectroscopic data and their absolute stereochemistries were determined in detail using a modified Mosher's method.

Antidepressant efficacy and safety of low-dose sertraline and standard-dose imipramine for the treatment of depression in older adults: results from a double-blind, randomized, controlled clinical trial.

This study compared the efficacy and tolerability of 150 mg/day imipramine and 50 mg/day sertraline for the treatment of a major depressive episode (DSM-IV) in older adults (N = 55) in an 8-week, randomized, double-blind, controlled clinical trial. Intention-to-treat analysis (last observation carried forwards) showed a reduction of 50% or more on the baseline scores of the Montgomery-Asberg Rating Scale (MADRS) in 60.7% and 55.6% of patients receiving imipramine and sertraline, respectively (p = .698). Full remission of symptoms (MADRS < 9) was observed in 50.0% and 51.8% of patients, respectively (p = .891). Side effects were more frequent among patients treated with imipramine (86.7%) than among patients treated with sertraline (42.1%) (p = .008). Dropout rates were high in both groups (46.4% and 29.6% respectively, p =.200). These results indicate that imipramine and sertraline are equally effective for the treatment of major depression in later life, although adverse reactions are more frequent among subjects treated with imipramine than with sertraline.

Validity of the Michigan Alcoholism Screening Test (MAST) for the detection of alcohol-related problems among male geriatric outpatients.

Alcoholism is a frequent and underdiagnosed mental health problem of later life. Its detection often relies on the use of screening instruments such as the Michigan Alcoholism Screening Test (MAST). The authors investigated the properties of the scale in a sample of 122 older adults recruited from a geriatric outpatient service in São Paulo, Brazil. Thirty-five subjects met criteria for the diagnosis of alcohol abuse or dependence according to DSM-III-R. The cutoff point 4/5 was associated with a sensitivity of 91.4%, specificity of 83.9%, and positive and negative predictive values of 69.6% and 96.0%, respectively. These results indicate that the MAST is a good screening test for the detection of alcohol abuse and dependence in an elderly male population and that the MAST should be used in combination with a questionnaire assessing the frequency/quantity of alcohol consumption to optimize the detection of cases and characterize their current drinking patterns.

Isolation of lignan glucosides and neolignan sulfate from the leaves of Glochidion zeylanicum (Gaertn) A. Juss.

Six lignan and neolignan derivatives (1-6) were isolated from the n-BuOH-soluble fraction of a MeOH extract of the leaves of Glochidion zeylanicum. On the basis of spectral data, their structures were elucidated to be (+)-isolarisiresinol 3a-O-beta-glucopyranoside (1), dihydrodehydrodiconiferyl alcohol 4-, 9- and 9'-O-beta-D-glucopyranosides (2-4, respectively), (+)-isolarisiresinol 2a-O-beta-D-glucopyranoside (5), and dihydrodehydrodiconiferyl alcohol 9-O-sulfate (6), and 5 and 6 were new compounds.

Antidepressant efficacy of sertraline and imipramine for the treatment of major depression in elderly outpatients.

CONTEXT: Most double-blind studies of efficacy and tolerability of sertraline as compared to tricyclics in the treatment of late-life major depression have used amitriptyline as a standard, leading to the inevitable conclusion that the former drug is better tolerated than the latter, with both being equally efficacious. OBJECTIVE: To compare the antidepressant efficacy and tolerability of sertraline (50 mg/day) and imipramine (150 mg/day) in the first 6 weeks of the treatment of major depression in the elderly. DESIGN: A randomized double-blind parallel study with 6 weeks of follow-up. SETTING: The psychogeriatric clinic at the Institute of Psychiatry, Hospital das Clínicas, Faculty of Medicine of the University of São Paulo. PARTICIPANTS: 55 severe and moderately depressed non-demented outpatients aged 60 years or more. INTERVENTION: Patients were assigned to sertraline 50 mg/day or imipramine 150 mg/day. MAIN MEASUREMENTS: CAMDEX interview. Psychiatric diagnosis followed the guidelines for "Major Depressive Episode" according to DSM-IV criteria. Severity of symptoms was evaluated using the "CGI" and "MADRS" scales. Cognitive state was assessed using the Mini-Mental State Examination. Side effects were assessed using the "Safetee-Up" schedule. RESULTS: Both groups had a significant decrease in depressive symptoms according to the MADRS scores after 6 weeks of treatment (P = 0.01). No significant differences between groups were detected regarding treatment outcome (t = 0.4; P = 0.7). Although the dropout rate was greater in the imipramine group, the overall tolerability among patients who completed the 6-week trial was similar in both test groups. CONCLUSIONS: Both sertraline and imipramine exhibited good efficacy and an acceptable side-effect profile for elderly depressed patients after 6 weeks of antidepressant treatment.

New megastigmane and tetraketide from the leaves of Euscaphis japonica.

New megastigmane (1) and tetraketide (2) were isolated from the leaves of Euscaphis japonica and the structures were elucidated by means of spectroscopic and chemical evidence.

Megastigmane, benzyl and phenethyl alcohol glycosides, and 4,4'-dimethoxy-beta-truxinic acid catalpol diester from the leaves of Premna subscandens MERR.

Extensive isolation work on the n-BuOH-soluble fraction obtained from the leaves of Premna subscandens, collected on Ishigaki island, Okinawa, afforded six compounds. Two were identified as megastigmane glucosides, 7-(3,5-dihydroxy-1,1,5-trimethylcyclohexylidene)-9-methylprop++ +-8-enyl 9-O-beta-D-glucopyranoside and 3-hydroxy-5,6-epoxy-beta-ionol 9-O-beta-D-glucopyranoside. The structures of the remaining four new compounds were elucidated to be a 2'-O-beta-D-apiofuranosyl derivative of 3-hydroxy-5,6-epoxy-beta-ionol 9-O-beta-D-glucopyranoside, named premnaionoside, benzyl alcohol beta-D-(2'-O-beta-D-xylopyranosyl)glucopyranoside, phenethyl alcohol beta-D-(2'-O-beta-D-glucopyranosyl)glucopyranoside, and 4,4'-dimethoxy-beta-truxinic acid catalpol diester by spectroscopic analyses.

Glochidionolactones A-F: butenolide glucosides from leaves of Glochidion zeylanicum (GAERTN) A. JUSS.

From the leaves of Glochidion zeylanicum, six new butenolide glucoside, named glochidionolactones A-F, were isolated along with a known related compound, phyllanthurinolactone. The structures of glochidionolactones A-D and F were elucidated mainly by spectroscopic analyses. The absolute stereochemistry of glochidionolactone E was established by X-ray crystallographic analysis.

[Scintigraphic study of gastric emptying and intragastric distribution of a solid meal: gender differences]. / Estudo do esvaziamento gástrico e da distribuição intragástrica de uma dieta sólida através da cintilografia: diferenças entre os sexos.

Gender-related differences in gastric emptying are still controversial. The aims of this study were: to confirm the sex-related difference in gastric emptying of a solid meal and to investigate its association with different patterns of meal distribution between the proximal and distal gastric compartments. Eighteen healthy volunteers (nine males, mean age 35 +/- 9 years; nine females, mean age: 41 +/- 11 years) were studied in the morning, after ingestion of the solid test-meal (an omelette labeled with 185MBq of 99mTc-sulfur colloid). Simultaneous anterior and posterior images of the stomach were acquired immediately after ingestion of the meal and every 10 minutes for 120 minutes. Time versus activity curves were obtained for the whole, proximal and distal stomach. Gastric T1/2 was longer in women (96.1 +/- 17.2 min) than in men (79.9 +/- 17.8 min; P = 0.02). The analysis of the meal distribution inside the stomach showed no differences between males and females in proximal gastric emptying, but the meal retention in the distal compartment was significantly increased among women (P = 0.04). In conclusion, gastric emptying of a solid meal is slower in pre-menopausal women than in age-matched men, probably due to an increased retention of the meal in the distal compartment. This should be taken into consideration to avoid misleading diagnosis of gastroparesis for female patients.

Hypodontia in primary dentition: a case report.

The prevalence, possible etiological factors and management of hypodontia in primary dentition are reviewed. A case of hypodontia involving the primary lower incisor is reported.

A collagen network formation effector from leaves of Premna subscandens.

As a part of the search for biologically active plant products, M cells, which form a collagen fiber network in vitro after a prolonged culture period, were used. The n-BuOH-soluble fraction of a methanol extract of leaves of Premna subscandens exhibited promotion of collagen network formation by M cells. Extensive isolation work guided by a bioassay afforded a phenylethanoid, acteoside, as an active compound.

Increased excretion of urinary transforming growth factor beta 1 in patients with diabetic nephropathy.

The accumulation of extracellular matrix in the glomeruli of human and experimental models of diabetic nephropathy is associated with disease progression. Transforming growth factor beta 1 (TGF-beta1), which is a multifunctional peptide growth factor, plays a key role in the synthesis of extracellular matrix protein in vitro, and the expression of TGF-beta1 is elevated in human and rat diabetic nephropathy. In this study, we measured the urinary TGF-beta1 excretion in 57 patients with non-insulin-dependent diabetes mellitus and in 20 healthy volunteers to examine whether the determination of urinary TGF-beta1 excretion would facilitate the evaluation of the degree of mesangial expansion in patients with diabetic nephropathy. Both active and total TGF-beta1 levels in 24-hour urine samples collected from patients with diabetes mellitus and normal controls were measured using an enzyme-linked immunosorbent assay. We observed a higher excretion of urinary TGF-beta1 in patients with diabetes mellitus than in normal controls. In addition, the urinary TGF-beta1 excretion was elevated in patients with severe mesangial expansion. These results suggest that urinary TGF-beta1 may represent one parameter that can be used to evaluate the progression of diabetic nephropathy.

Measurement of plasma and urinary adrenomedullin in patients with IgA nephropathy.

In this study, we measured plasma and urinary adrenomedullin (AM) concentrations in 47 patients with IgA nephropathy. Controls were 39 healthy volunteers. Plasma and urinary AM values were measured by specific radioimmunoassay. The plasma AM concentrations were higher, and the urinary AM levels were lower in patients with IgA nephropathy than in healthy volunteers. Plasma AM concentrations showed a positive correlation with serum creatinine and blood urea nitrogen, whereas urinary AM levels correlated negatively with serum creatinine and blood urea nitrogen. The plasma AM concentrations showed a positive correlation with fractional excretions of sodium and potassium. Renal biopsy specimens of patients without renal failure were scored for activity (percentage of glomeruli demonstrating cellular crescent formation, degree of mesangial proliferation and interstitial infiltration; total score = 9). Urinary AM levels were shown to be lower in the group with a high activity (score 3-9) as compared with the group with a low activity (score 0-2) based on renal biopsy. Thus, urinary levels of AM are affected by the degree of the activity in IgA nephropathy, and AM may participate in the pathophysiology of IgA nephropathy.

Alcoholism in a geriatric outpatient clinic of São Paulo-Brazil.

Alcohol abuse and dependence are an increasing health problem among the elderly, but there is only scanty information about their prevalence and associated risk factors in developing countries. The authors set out to evaluate the prevalence and associated clinical/demographic features of alcoholism in a sample of male elderly subjects attending a Geriatric Primary Health Outpatient Clinic in a State University Hospital in the City of São Paulo-Brazil. Three hundred four patients were assessed with the Brazilian version of the Michigan Alcoholism Screening Test and a semistructured questionnaire designed to investigate associated features. Lifetime alcoholism was present in 15.1% of the sample, although only 4.3% were active drinkers. Patients classified as "cases" were younger than their nonalcoholic counterparts (70.61 vs. 73.31), and there was a mild, though not significant, excess of Blacks and Mulattos among the former (32.6% vs. 15.9%). Cases were also more likely to rely on their family for financial support (59.0% vs. 43.5%) and to acknowledge a positive family history of alcoholism (51.4% vs. 31.2%). Alcohol abuse or dependence was further associated with heavy smoking (58.7% vs. 44.0%). The authors concluded that alcoholism in this Brazilian elderly sample was likely to be associated with an earlier age at onset of medical problems, financial dependence, Black/Mulatto race, smoking, and positive family history of alcohol abuse/dependence. The authors suggest that the use of standardized methods of assessment of alcoholism in general medical settings may increase the detection of cases and contribute to improved health measures for the management of these patients.

Glycosides of megastigmane and of the simple alcohols from Alangium premnifolium.

From the water-soluble fraction of a methanol extract of leaves of Alangium premnifolium, two new megastigmane glycosides, alangionosides N and O, along with three known megastigmane glycosides, dendranthemoside A and alangionosides A and B, were isolated. Shimaurinosides A and B, xylopyranosyl(1-->6)glucopyranosides of simple alcohols were also found to be constituents of the water-soluble fraction. Structures were determined by spectroscopic analyses.