Biomarkers for personalised prevention of chronic diseases: a common protocol for three rapid scoping reviews.

INTRODUCTION: Personalised prevention aims to delay or avoid disease occurrence, progression, and recurrence of disease through the adoption of targeted interventions that consider the individual biological, including genetic data, environmental and behavioural characteristics, as well as the socio-cultural context. This protocol summarises the main features of a rapid scoping review to show the research landscape on biomarkers or a combination of biomarkers that may help to better identify subgroups of individuals with different risks of developing specific diseases in which specific preventive strategies could have an impact on clinical outcomes. This review is part of the "Personalised Prevention Roadmap for the future HEalThcare" (PROPHET) project, which seeks to highlight the gaps in current personalised preventive approaches, in order to develop a Strategic Research and Innovation Agenda for the European Union. OBJECTIVE: To systematically map and review the evidence of biomarkers that are available or under development in cancer, cardiovascular and neurodegenerative diseases that are or can be used for personalised prevention in the general population, in clinical or public health settings. METHODS: Three rapid scoping reviews are being conducted in parallel (February-June 2023), based on a common framework with some adjustments to suit each specific condition (cancer, cardiovascular or neurodegenerative diseases). Medline and Embase will be searched to identify publications between 2020 and 2023. To shorten the time frames, 10% of the papers will undergo screening by two reviewers and only English-language papers will be considered. The following information will be extracted by two reviewers from all the publications selected for inclusion: source type, citation details, country, inclusion/exclusion criteria (population, concept, context, type of evidence source), study methods, and key findings relevant to the review question/s. The selection criteria and the extraction sheet will be pre-tested. Relevant biomarkers for risk prediction and stratification will be recorded. Results will be presented graphically using an evidence map. INCLUSION CRITERIA: Population: general adult populations or adults from specific pre-defined high-risk subgroups; concept: all studies focusing on molecular, cellular, physiological, or imaging biomarkers used for individualised primary or secondary prevention of the diseases of interest; context: clinical or public health settings. SYSTEMATIC REVIEW REGISTRATION: https://doi.org/10.17605/OSF.IO/7JRWD (OSF registration DOI).

Application of the office or home computer to searching the medical literature.

Search of the medical literature has, until recently, most often been conducted by medical librarians. The recent development of "user friendly" systems and competition among an increasing number of commercial and non-commercial vendors now provide the opportunity to personally conduct literature searches using a home or office computer without enormous investment in time, training or equipment. Hardware requirements and general principles of computerized literature searching are described, and the various services available for individual subscription are summarized, including National Library of Medicine (NLM) MEDLINE; Bibliographic Retrieval Services (BRS) and BRS/Saunders Colleague; PaperChase; Dialog/Knowledge Index; American Medical Association (AMA) Minet; and MEDIS.

In situ oxidation-imine formation-reduction routes from alcohols to amines.

Manganese dioxide is employed as an in situ oxidant for the one-pot conversion of alcohols into imines. In combination with polymer-supported cyanoborohydride (PSCBH), a one-pot oxidation-imine formation-reduction sequence is reported. This procedure enables alcohols to be converted directly into both secondary and tertiary amines.

'Cepacia syndrome' with Burkholderia multivorans, 9 years after initial colonization.

A 16-year-old boy with cystic fibrosis developed 'cepacia syndrome' 9 years after the first isolation of Burkholderia multivorans. It is important to recognise that 'cepacia syndrome' is not restricted to those infected with genomovar type III strains and that rapid, irreversible clinical decline can occur many years after the 1st isolation of Burkholderia cepacia complex (Bcc).

Transparahippocampal selective amygdalohippocampectomy in children and adolescents: efficacy of the procedure and cognitive morbidity in patients.

OBJECT: Unilateral resection of the hippocampus and amygdala can be used to treat medically intractable mesial temporal lobe seizures. To date seizure outcome and the extent of cognitive morbidity have been unknown in children following the transparahippocampal variation of selective amygdalohippocampectomy (TSA), which prompted the present prospective study. METHODS: Preoperative examinations and outcomes in 22 consecutive children and adolescents who underwent TSA were studied. Cognitive and psychological morbidity were assessed using standard neuropsychological instruments. The authors evaluated relationships between seizure control and cognitive morbidity and 13 and nine clinical variables, respectively. Seizure control was achieved in 11 (65%) of 17 patients (>2 years follow up). Among 13 clinical variables, the only preoperative finding that had a significant bearing on seizure control was the presence of unilateral hypometabolism, which could be observed on [18F]fluorodeoxyglucose-positron emission tomography scans (p<0.001). Patients with seizure control showed significant improvements in verbal and full scale intelligence quotients (both p = 0.05). Patients with longer preoperative durations of seizures exhibited more cognitive impairment that persisted postoperatively. Cognitive outcome analysis based on nine clinical factors revealed no significant difference in cognitive parameters postoperatively, except that significant improvement occurred in rote verbal memory scores among patients who underwent right-sided TSA (p = 0.01). Individually, 81% of the children achieved significant improvement in at least one of seven cognitive parameters, and 52% had stable or improved scores in all parameters. CONCLUSIONS: The results indicate that TSA is a safe effective approach for the treatment of medically intractable mesial temporal lobe seizures in children with minimum effect on cognitive morbidity. Given that the literature suggests that children suffer progressive cognitive morbidity from persistent seizures, the results of this study support early surgical intervention for this group of children.

Silica-bound complexing agents: some aspects of synthesis, stability and pore size.

A number of factors related to the metal-ion reactivity of silica-bound complexing agents are discussed. The metal-uptake capacity of alkylamines immobilized on silica is shown to be reduced by hydrolysis of bound ligand from the surface, by protonation in aqueous buffers, and by an apparent air oxidation of the amine group or other deactivation process. A one-step silylation reaction using triethoxysilylpropyl-p-nitrobenzamide is shown to produce nitrobenzamide silica gel (NBSG) and azo-coupled material equivalent to that obtained by the former two-step process. Significant time saving is realized. Organic solvent washing of the NBSG, and the azo-coupled chelating agents derived from it, removes organic matter from the surface. Adsorbed or weakly bound polymers or oligomers present in the original silane or formed during the silylation are apparently dissolved slowly by these washing solvents. Finally, metal uptake (and presumably surface coverage), expressed as mumole m (2), of a series of 8-quinolinol controlled-pore glasses was found to decrease with decrease in pore size.

The use of splints in the treatment of joint stiffness: biologic rationale and an algorithm for making clinical decisions.

The purpose of this article are (1) to discuss the rationale for using splints to increase range of motion (ROM) and (2) to describe an algorithm that can guide therapists' clinical decisions when splints are used to treat patients who have limited ROM. The primary rationale for using splints is to apply relatively long periods of tensile stress to shortened connective tissues to induce tissue lengthening through biologic remodeling. The process of remodeling is contrasted with more temporary mechanical phenomena that occur in biologic tissues. The proposed algorithm guides the use of splints based on measurements of pain and ROM. We describe three variables of splint use that may be adjusted: frequency, duration, and intensity. The relative importance of each of these variables is discussed. The algorithm is not joint or injury specific and requires continual modification of splint use based on a patient's response to treatment. Deciding which patients are appropriate for end-range splinting and deciding when to discontinue splint use are also discussed.

The effect of tissue disaggregation methods on the clonogenicity of solid human tumor cells.

The effect of mechanical, enzymatic and combined disaggregations on the same tumor tissue (n = 154) to define variables related to clonogenic efficiency (CE) of human tumor clonogenic assay (HTCA) was examined. Overall, CE was highly associated with the percentage of malignant cells in the inoculative suspensions (P less than 0.001) and the total cell concentration plated (P = 0.03). However, there was no significant correlation between CE and the disaggregation method, type of tumor, cell viability, proportion of macrophages in the inoculum, or length of incubation (10 or 20 days). In addition, a higher CE was found in some nonadherent fractions when comparing the CE of the original plating suspensions to that of their nonadherent fractions. It is concluded that mechanical disaggregation is the simplest technique for obtaining the highest yield of malignant cells, which is a decisive factor for colony growth, and that an incubation time of 10 days and 1 x 10(6) cells per plate is the best condition for the human tumor clonogenic assay.

Effective treatment of Chlamydia trachomatis infection during pregnancy to prevent perinatal and infant complications.

Chlamydia trachomatis is the most prevalent cause of sexually transmitted disease in the United States today. Prenatal health care providers must learn to recognize and effectively treat chlamydial infection in order to help prevent serious consequences in the pregnant woman and in the neonate. This article discusses the diagnosis and treatment of chlamydial infection during pregnancy and during the neonatal period. Patient education of women infected during pregnancy should include guidelines for helping parents and care providers monitor the neonate for signs of conjunctivitis and pneumonia.

All-sky LIGO search for periodic gravitational waves in the early fifth-science-run data.

We report on an all-sky search with the LIGO detectors for periodic gravitational waves in the frequency range 50-1100 Hz and with the frequency's time derivative in the range -5 x 10{-9}-0 Hz s{-1}. Data from the first eight months of the fifth LIGO science run (S5) have been used in this search, which is based on a semicoherent method (PowerFlux) of summing strain power. Observing no evidence of periodic gravitational radiation, we report 95% confidence-level upper limits on radiation emitted by any unknown isolated rotating neutron stars within the search range. Strain limits below 10{-24} are obtained over a 200-Hz band, and the sensitivity improvement over previous searches increases the spatial volume sampled by an average factor of about 100 over the entire search band. For a neutron star with nominal equatorial ellipticity of 10{-6}, the search is sensitive to distances as great as 500 pc.

Search for gravitational-wave bursts from soft gamma repeaters.

We present a LIGO search for short-duration gravitational waves (GWs) associated with soft gamma ray repeater (SGR) bursts. This is the first search sensitive to neutron star f modes, usually considered the most efficient GW emitting modes. We find no evidence of GWs associated with any SGR burst in a sample consisting of the 27 Dec. 2004 giant flare from SGR 1806-20 and 190 lesser events from SGR 1806-20 and SGR 1900+14. The unprecedented sensitivity of the detectors allows us to set the most stringent limits on transient GW amplitudes published to date. We find upper limit estimates on the model-dependent isotropic GW emission energies (at a nominal distance of 10 kpc) between 3x10;{45} and 9x10;{52} erg depending on waveform type, detector antenna factors and noise characteristics at the time of the burst. These upper limits are within the theoretically predicted range of some SGR models.

Upper limits on a stochastic background of gravitational waves.

The Laser Interferometer Gravitational-Wave Observatory has performed a third science run with much improved sensitivities of all three interferometers. We present an analysis of approximately 200 hours of data acquired during this run, used to search for a stochastic background of gravitational radiation. We place upper bounds on the energy density stored as gravitational radiation for three different spectral power laws. For the flat spectrum, our limit of omega0 < 8.4 x 10(-4) in the 69-156 Hz band is approximately 10(5) times lower than the previous result in this frequency range.

Limits on gravitational-wave emission from selected pulsars using LIGO data.

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10(-5) for the four closest pulsars.

Neutralized Direct-Acid-Set Whey as an Extender for a Chocolate-Flavored Dairy Drink 1.

A chocolate-flavored dairy drink was prepared in which four parts of neutralized direct-acid-set whey and six parts of whole milk were combined with 1.44% chocolate flavoring, 4.5% sugar and 0.2% nonfat-dry milk. The extended chocolate-flavored drink was compared with a conventional chocolate-flavored low-fat milk made with the same formulation except skimmilk replaced neutralized whey and no nonfat-dry milk was added. Both products were heated to 80 C and mixed 2 min in an institutional Waring blender to disburse salts from neutralized whey. pasteurized at 80 C for 35 min and cooled immediately to 5 C. Sedimentation. viscosity, pH and consumer acceptability were determined. No sedimentation occurred after 7 days of storage, but after 10 days about 5.3% sediment by volume was observed in both drinks upon centrifugation. After 7 days at 4 C, the whey-extended chocolate drink had a 4% by volume watery layer that increased to 4.5% after 10 days. Maximum viscosities of 47 and 49 centipoise, respectively, were obtained after 5 days at 4 C for the extended and conventional chocolate-flavored low-fat milk. Viscosities declined to 26-27 centipoise after 10 days. Twenty-two of a consumer panel of 37 preferred the whey drink over the conventional, and seven expressed no preference, judging by a combined preference/triangle test. When data from the triangle taste test were subjected to a statistical analyses, the probability for preference was .47 for the whey drink, .30 control and .21 no preference. There was no difference in acceptability (p > 0.05).

Antiemetic efficacy of single-dose oral granisetron (1 mg vs 2 mg) with moderately emetogenic chemotherapy.

PURPOSE: To compare the efficacy of oral granisetron, 1 mg and 2 mg, administered as one dose in patients who receive moderately emetogenic chemotherapy. PATIENTS AND METHODS: Chemotherapy-naïve patients, scheduled to receive intravenous cyclophosphamide (500 to 1200 mg/m2) or carboplatin (> or = 300 mg/m2), were stratified by dexamethasone/methylprednisolone use (+ DEX, n = 92) or nonuse (- DEX, n = 5). Patients were randomized to one dose of either 1 mg (n = 48) or 2 mg (n = 49) of granisetron administered 60 minutes before chemotherapy. Known important prognostic variables (gender, age, alcohol) were well balanced between groups. RESULTS: Using the most rigorous criterion of total control (no emetic episodes, no nausea, no rescue therapy during the first 24 hours), response rates were 54.2% (26/48) and 57.1% (28/49) in patients receiving 1 mg and 2 mg of granisetron, respectively (95% confidence interval, -0.17, 0.23). Total control rates in patients who received 1 mg and 2 mg of granisetron + DEX were also comparable: 57.8% (26/45) and 55.3% (26/47), respectively. Response rates were similar for the parameters of nausea, emesis, and complete response (no emetic episodes, no more than mild nausea, no antiemetic rescue). Among all patients, one (2.1%) who received 1 mg of granisetron and three (6.1%) who received 2 mg experienced severe nausea. The proportions of 1- and 2-mg-treated patients who received rescue therapy within the first 24 hours were 31.3% (15/48) and 34.7% (17/49), respectively. Reported adverse experiences were generally mild in severity. DISCUSSION: The results of this trial demonstrate good control of emesis with a single 1-mg dose of oral granisetron, with efficacy that compares favorably with that of a 2-mg dose.

Radiation dose-dependent variations of micronuclei production in cytochalasin B-blocked human lymphocytes.

Using the cytokinesis-block technique, lymphocytes from healthy volunteers (n = 9) were evaluated for 1) the radiation dose-response curve for micronuclei (MN) expression; 2) technique variables on the yield of MN; and 3) the shortest lymphocyte incubation time required for the MN assay. We found that the best fitting of relationships between increasing MN production and increasing irradiation dose (0-4.0 Gy) was the linear-quadratic model as expressed by the yield equation Y = C+alpha D+beta D2 (P = 0.0003). When lymphocytes were irradiated in vitro with 2.0 Gy and harvested at various time intervals, MN increased during the entire 84 hr culture time. The radiation caused a division delay in lymphocyte as indicated by an increased frequency of mononucleated cells and a decreased number of mitotic indices. The data showed that a shortened culture time (60 hr) for the MN assay is possible and that binucleated cells with > or = 3 MN were found only in cells irradiated at > or = 2.0 Gy. These findings suggest that scoring of MN in lymphocytes may be a practical biological dosimeter for the rapid screening of accidental radiation exposure victims, especially when their clinical manifestations are not obvious.

The size of small cell lung carcinoma cells. Ratio to lymphocytes and correlation with specimen size and crush artifact.

The size of small cell lung carcinoma (SCLC) cells has often been ambiguously defined as one and a half to four times that of a lymphocyte. The purpose of this study was to determine the ratio of nuclear diameter (ND) of SCLC cells to that of lymphocytes in the same tissue sections and to assess whether the size of SCLC cells correlates with the size of tumor specimens and crush artifact. The overall mean ND (microns +/- SD) of SCLC cells was 9.2 +/- 2.1, found in 36 oat cell carcinomas (OAT, 1,800 nuclei) and 16 intermediate cell carcinomas (INT, 800 nuclei). The mean ND of OAT and INT cells was 8.1 +/- 1.3 and 11.6 +/- 1.5, respectively. The mean ND of lymphocytes (2,600 nuclei) was 5.2 +/- 0.3. The overall mean of ND ratios (+/- SD) between SCLC cells and lymphocytes was 1.8 +/- 0.4 (median, 1.7), 1.6 +/- 0.2 for OAT and 2.2 +/- 0.3 for INT. The mean size of the 52 SCLC biopsy specimens was 0.6 +/- 0.9 cm. Of all the biopsies, 84.6% (n = 44) showed various degrees of tissue crushing. The ND of SCLC cells was associated with specimen size (P = .004) and the degree of tissue crushing (P = .001). Therefore, our findings further support the hypothesis that OAT should be considered the effect of artifact rather than a true variant of SCLC and that the ND of SCLC cells is approximately two times that of lymphocytes.