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Results for “protocol optimization”

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PubMed1992

Impaired response to hepatitis B vaccine in HIV infected children.

Eighteen human immunodeficiency virus (HIV) vertically infected children (HIV group) and 33 seroreverted children (SR group), who had completed hepatitis B vaccination (Engerix B, 20 micrograms dose) were studied. Four out of 18 (22%) HIV children failed to develop protective antibody levels (anti-HBs titres less than 10 mIU ml-1) compared with 1 out of 33 (3%) SR children (p less than 0.05). Magnitude of response among HIV children was significantly lower than among SR children. In HIV children the probability that anti-HBs titres persist above the protective levels was significantly lower than in the SR group at any time during the 24 month follow-up. These results show that HIV children have a suboptimal response to hepatitis B immunization and the protection is less durable. Further studies are needed to determine the optimal protocol for hepatitis B immunization in HIV children.

Child, Preschool↗

PubMed1983

Effects of strain, sex, route of administration and partial hepatectomy on the induction by chemical carcinogens of gamma-glutamyltranspeptidase foci in rat liver.

The incidence of gamma-glutamyltranspeptidase (GGT)-positive foci induced by 0.3 mmol/kg diethylnitrosamine (DENA) followed by promotion with 500 ppm sodium phenobarbital in drinking water and was the same in Fischer 344, Sprague-Dawley and Wistar-Lewis rats. There was no difference in the level of GGT-foci initiated by DENA, 7,12-dimethylbenz[a]-anthracene (DMBA), or 1,2-dimethylhydrazine (DMH) followed by promotion with phenobarbital with respect to sex or route of administration including gavage and intraperitoneal injection. Maximal stimulation by partial hepatectomy of DENA initiation of GGT-foci occurred when the DENA was administered 18 h after the operation. Our results indicate that the optimal protocol for the rat liver foci assay consists of using partial hepatectomized rats of 1 of the 3 strains and of either sex. The test substance should be administered by either gavage or intraperitoneal injection so that maximal DNA binding coincides with the maximal rate of DNA replication resulting from partial hepatectomy.

Animals↗

PubMed1991

Hybridization methods for DNA sequencing.

I have conducted a general analysis of the practicability of using oligonucleotide hybridization to sequence DNA. Any DNA sequence may be sequenced by hybridization with a complete panel of oligonucleotides. However, sequencing DNA segments over 2 kb long requires an unrealistic number of hybridization reactions. The optimal protocol is to hybridize 7-mer or 8-mer mixed oligonucleotide probes to immobilized DNA fragments 80 bp long: should this prove impractical, hybridization of labeled 270-bp fragments to immobilized mixed 10-mers is a potential alternative. Both protocols require no more experiments to sequence large regions of DNA than conventional m13-based sequencing and are much easier to automate, thus reducing the requirements for skilled personnel. In the ideal case, hybridization sequencing reduces the number of experiments required to sequence megabase DNA by 90%.

Base Sequence↗

PubMed2026

Non-tobacco nicotine dependence and postoperative complications after total ankle arthroplasty: A propensity-matched cohort study.

BACKGROUND: The clinical impact of non-tobacco nicotine dependence (NTND) is poorly defined. This study evaluated the association between NTND and complications following total ankle arthroplasty (TAA). METHODS: A retrospective cohort study using the TriNetX Research Network was performed. Adults undergoing primary TAA (Current Procedural Terminology [CPT] 27702) between 2010 and 2025 were included. Patients were categorized into NTND (International Classification of Diseases, Tenth Revision [ICD-10]: F17, excluding tobacco-specific codes) and nonsmoker cohorts. Propensity score matching (1:1) yielded 939 NTND patients and 939 controls. Ninety-day medical and wound complications and ≥ 2-year mechanical outcomes were assessed. RESULTS: NTND patients had higher rates of 90-day readmission (11.7% vs 6.5%; OR 1.9), wound disruption (4.3% vs 2.6%; OR 1.7), surgical site infection (3.1% vs 1.6%; OR 2.0), and sepsis (2.4% vs 1.1%; OR 2.3). At a minimum 2-year follow-up, NTND was not associated with increased risk of mechanical complications. CONCLUSION: These findings challenge the assumption that smokeless nicotine products are benign in the perioperative setting and support incorporating NTND screening and cessation counseling into preoperative optimization protocols. Future prospective studies are warranted to further characterize the dose-dependent effects of non-tobacco nicotine exposure and to evaluate the impact of perioperative cessation strategies on outcomes following TAA. LEVEL OF EVIDENCE: IV.

Humans↗

PubMed2026

Clinical applications of digital twin technology in In Vitro Fertilisation.

BACKGROUND: Digital twin technology, originating from aerospace and manufacturing industries, has emerged as a transformative tool in healthcare. In vitro fertilisation (IVF) faces persistent challenges including suboptimal embryo selection, unpredictable treatment outcomes, and limited personalisation of protocols. Despite advances in assisted reproductive technology, existing literature exhibits fragmentation: artificial intelligence applications in embryo selection, ovarian stimulation, and endometrial assessment have been developed independently without systematic integration into comprehensive treatment frameworks. Digital twin technology offers unprecedented opportunities to create virtual replicas of biological systems, enabling real-time monitoring, predictive modelling, and personalised treatment strategies. AIM: This narrative review aims to critically examine the current applications of digital twin technology in IVF, evaluate its potential benefits and limitations, synthesize existing evidence into an integrative conceptual model, and identify future directions for implementation in reproductive medicine. METHOD: A comprehensive narrative review was conducted using PubMed, Scopus, Web of Science, and IEEE Xplore databases. A narrative review approach was selected over systematic review to accommodate the heterogeneity of evidence types in this emerging field, including theoretical frameworks, simulation studies, and proof-of-concept implementations that would be excluded from systematic reviews. Search terms included "digital twin," "IVF," "in vitro fertilisation," "assisted reproductive technology," "embryo selection," and "predictive modelling." Studies published between 2015 and 2025 were included, focusing on original research articles, systematic reviews, and proof-of-concept studies describing digital twin applications in reproductive medicine. RESULTS: Digital twin technology in IVF demonstrates significant potential across multiple domains including embryo development simulation, ovarian response prediction, endometrial receptivity modelling, and personalised stimulation protocols. Current applications integrate artificial intelligence, machine learning algorithms, time-lapse imaging, and omics data to create comprehensive virtual models. Early evidence suggests improvements in embryo selection accuracy, ovarian response prediction, and treatment protocol optimization, though large-scale randomized controlled trials remain limited. Implementation challenges include data integration complexity, computational requirements, regulatory considerations, and validation requirements. CONCLUSION: Digital twin technology represents a paradigm shift in IVF practice, offering personalised, predictive, and precision medicine approaches. This review synthesizes existing evidence to propose an integrative conceptual model for digital twin implementation across the IVF treatment spectrum, identifies critical knowledge gaps, and establishes research priorities to advance clinical translation. Despite current limitations, continued advancement promises improved success rates and patient outcomes.

Humans↗

PubMed2026

Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR = 0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR = 0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR = 0.68, 95%-CI: 0.53-0.86) and event-free survival (HR = 0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3 years was significantly lower with haplo-cord (OR = 0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

Humans↗

PubMed1998

A quantitative histometric murine in vivo model of radiation-induced oral mucositis.

Gastrointestinal toxicity is a limiting factor in the effectiveness of cancer therapy. This toxicity is most visible in the mouth. There is considerable interest in developing strategies involving growth-factor manipulation of the epithelial stem cells to afford protection to these cells during treatment and/or to speed up the regenerative process following treatment. In order for this to be achieved, studies have to be undertaken in animal systems to demonstrate the proof of principle and determine optimal protocols. Here, a murine model for oral mucositis based on measurements of tissue cellularity at various times after exposure to radiation was used to investigate cytotoxicity. Several sites in the mouth were analysed and the pronounced circadian rhythm in these various epithelial sites determined. The circadian rhythm is important in that it would determine the timing of administration of growth factors. A microscope with an interactive computer was used to define areas of epithelium and lengths of basal layer, within which, and along which, the total number of cell nuclei was determined over a range of times following exposure to 10, 20 and 30 Gy of X-rays. For various practical reasons, the ventral surface of the tongue was identified as the most appropriate tissue to analyse. Here, measurements of cellularity reached minimum values between 6 and 8 days following 20 Gy. Labelling of S-phase cells demonstrated foci of regeneration and a burst of proliferative regeneration that commenced at about 5 days and reached peak values at 8 days after irradiation. This burst of regenerative proliferation was coincident with the minimum in tissue cellularity on about day 8. The lower dose of radiation (10 Gy) had minimal effects on cellularity: after the higher dose (30 Gy), there was clearly a more severe level of cellular depletion. This quantitative model of oral mucositis could be used to study the effects of other cytotoxics, including combinations of agents, and the potential role of growth factors to reduce the severity of the cellular depletion and to speed up the kinetics of regeneration.

Animals↗

PubMed1996

Distinct local anesthetic affinities in Na+ channel subtypes.

Lidocaine is a widely used local anesthetic and antiarrhythmic drug that is believed to exert its clinically important action by blocking voltage-gated Na+ channels. Studies of Na+ channels from different species and tissues and the complexity of the drug-channel interaction create difficulty in understanding whether there are Na+ channel isoform specific differences in the affinity for lidocaine. Clinical usage suggests that lidocaine selectively targets cardiac Na+ channels because it is effective for the treatment of arrhythmias with few side effects on muscle or neuronal channels except at higher concentrations. One possibility for this selectivity is an intrinsically higher drug-binding affinity of the cardiac isoform. Alternatively, lidocaine may appear cardioselective because of preferential interactions with the inactivated state of the Na+ channel, which is occupied much longer in cardiac cells. Recombinant skeletal muscle (hSkM1) and cardiac sodium channels (hH1) were studied under identical conditions, with a whole-cell voltage clamp used to distinguish the mechanisms of lidocaine block. Tonic block at high concentrations of lidocaine (0.1 mM) was greater in hH1 than in hSkM1. This was also true for use-dependent block, for which 25-microM lidocaine produced an inhibition in hH1 equivalent to 0.1 mM in the skeletal muscle isoform. Pulse protocols optimized to explore inactivated-state block revealed that hSkM1 was five to eight times less sensitive to block by lidocaine than was hH1. The results also indicate that relatively more open-state block occurs in hSkM1. Thus, the cardiac sodium channel is intrinsically more sensitive to inhibition by lidocaine.

Anesthetics, Local↗

PubMed1998

Distribution of the endothelial constitutive nitric oxide synthase in the developing rat brain: an immunohistochemical study.

The present study deals with the distribution of endothelial constitutive nitric oxide synthase (ecNOS) in the developing rat brain using optimized protocols for preparation and fixation and the tyramide-signal-amplification technique. The immunostaining patterns of a monoclonal antibody against ecNOS are compared with results obtained with a rat pan-endothelial marker, the monoclonal RECA-1 antibody. It is shown that ecNOS is present in the endothelial lining of all types of blood vessels and the choroid plexuses of the rat brain from the beginning of vasculogenesis at embryonic day 11 until adulthood (75 weeks). The same is true for RECA-1 immunoreactivity, that was demonstrated in the developmental brain vasculature for the first time. Both antigens expressed identical immunostaining patterns. At all investigated stages of brain development neither ecNOS negative blood vessels nor ecNOS positive non-endothelial cells, e.g., neurons, were found. The data indicate that ecNOS is involved in the embryonic angiogenesis and the regulation of hemodynamic functions of brain vasculature throughout the individual life.

Animals↗

PubMed1991

Comparison of silica-based cyanopropyl and octyl reversed-phase packings for the separation of peptides and proteins.

The performance of a silica-based C8 packing was compared with that of a less hydrophobic, silica-based cyanopropyl (CN) packing during their application to reversed-phase high-performance liquid chromatography (linear trifluoroacetic acid-water to trifluoroacetic acid-acetonitrile gradients) of peptides and proteins. It was found that: (1) the CN column showed excellent selectivity for peptides which varied widely in hydrophobicity and peptide chain length; (2) peptides which could not be resolved easily on the C8 column were widely separated on the CN column; (3) certain mixtures of peptides and small organic molecules which could not be resolved on the C8 column were completely separated on the CN column; (4) impurities arising from solid-phase peptide synthesis were resolved by a wide margin on the CN column, unlike on the C8 column, where these compounds were eluted very close to the peptide product of interest: and (5) specific protein mixtures exhibited superior resolution and peak shape on the CN column compared with the C8 column. The results clearly demonstrate the effectiveness of employing stationary phases of different selectivities (as opposed to the more common optimization protocol of manipulating the mobile phase) for specific peptide and protein applications, an approach underestimated in the past.

Amino Acid Sequence↗

PubMed1997

Optimization of the sulforhodamine B colorimetric assay.

Sulforhodamine B (SRB) protein staining has been widely used for cell proliferation and chemosensitivity testing, substituting for tetrazolium-based assays. However, the cell fixation step in the original assay is subject to error. We tested whether aspiration of medium with an automatic microplate multiwash device prior to fixation improves the method for adherent cells. A panel of adherent cell lines was used. Signal-to-noise ratios were significantly increased in the new assay. Coefficients of variation (CV) between replicate wells were significantly lower especially at lower cell densities. The linearity of the method improved, with absolute linearity over the whole range of cell densities. The aspiration procedure dislodged only negligible numbers of cells. Cytotoxicity testing using the cytotoxic agent paclitaxel showed no IC50 (50% inhibitory concentration) differences between the new and original methods but a better CV was associated with the optimized protocol. We conclude that aspiration of the growth medium prior to fixing comprises a safe and reliable practice which improves CV, linearity and the signal-to-noise ratio of the SRB assay.

Animals↗

PubMed1985

Bacillus Calmette-Guerin immunotherapy for bladder cancer.

Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. While the optimal protocol for bacillus Calmette-Guerin remains to be determined, experience with 92 randomized and 30 nonrandomized (high risk) patients followed for up to 5 years provides information that may improve future protocols. Side effects of bacillus Calmette-Guerin are observed to increase with increasing frequency and duration of treatment. The protection from tumor recurrence has persisted: only 6 of 30 patients (20 per cent) treated with bacillus Calmette-Guerin have had recurrent tumor compared to 14 of 27 controls (52 per cent, p equals 0.008, chi-square test), and mean time to recurrence increased from 24 to 48 months (p less than 0.005, Savage). Skin test reactivity to purified protein derivative is particularly useful in predicting response to bacillus Calmette-Guerin immunotherapy. Currently, 60 patients have been randomized to receive bacillus Calmette-Guerin immunotherapy and only 1 of 22 patients (4.5 per cent) in whom the purified protein derivative skin test results converted from negative to positive has had recurrent tumor, compared to 12 recurrences (32 per cent) in patients whose skin tests were positive before treatment or failed to convert following treatment (p equals 0.014, chi-square). Seven recurrences (33 per cent) developed in 21 patients whose skin tests remained negative (p equals 0.015) and 5 recurrences (29 per cent) developed in 17 patients whose tests previously were positive (p equals 0.068, Fisher's test, not significant). The benefit of percutaneous bacillus Calmette-Guerin is suggested by the observations that the recurrence rate in patients treated with intravesical bacillus Calmette-Guerin alone is 40 per cent, and all 7 patients whose purified protein derivative skin tests were negative continued to have negative results when percutaneous bacillus Calmette-Guerin was omitted (p equals 0.003). Among high risk patients a marked decrease in or complete prevention of recurrent tumor was observed in 82 per cent of 22 patients treated previously with chemotherapy and 11 of 14 (78 per cent) with carcinoma in situ have had a complete response.

Aged↗

PubMed1983

Simultaneous sonographic demonstration of tumor thrombus in the inferior vena cava and patient main renal vein in renal carcinoma.

With the introduction of new imaging modalities the optimal protocol for the evaluation of renal tumors is under close review. Angiographers frequently are faced with the question of whether to proceed to inferior venacavography following a selective renal angiogram that demonstrates a patent renal vein. We report a case of renal cell carcinoma in which the main renal vein was shown by ultrasound to be unequivocally patent but at the same time there was considerable tumor extension into the inferior vena cava. The necessity of full examination of the inferior vena cava, either by venacavography or ultrasound, in all cases of renal cell carcinoma is stressed.

Adenocarcinoma↗

PubMed1994

Towards a standard method to demonstrate adenylate cyclase activity at the electron microscopical level.

The ventral epidermis of the frog Rana fuscigula is a typical tight epithelium which acts as a functional syncytium in the active transepithelial transport of sodium ions. Transport across this epithelium is regulated by cyclic adenosine monophosphate (cAMP). This study was undertaken to formulate an optimal protocol for the localization, within this epithelium, of adenylate cyclase; the enzyme involved in cAMP synthesis. The ventral epithelium of R. fuscigula was collagenase treated and processed using five different fixation/incubation protocols. The components of a basal incubating medium were modified by changing the localizing agent, adding adenylate cyclase stimulators and inhibitors of other enzymes. Control incubations undertaken included a) leaving the substrate out, b) prior heat inactivation of the enzyme, c) specific blockers and d) incubation for alkaline phosphatase as an alternative enzyme. The samples were then processed for electron microscopy. Localization of adenylate cyclase was best obtained, when fixing the tissue after incubation for 30 min at 37 degrees C. The medium that gave the best and most consistent localization contained magnesium chloride; as a required ion, theophylline, dithiothreitol, ouabain, levamisole; as enzyme inhibitors, forskolin; as a stimulator of adenylate cyclase, lead nitrate; as the capture agent and column purified adenylyl imidodiphosphate; as the substrate.

Adenylyl Cyclase Inhibitors↗

PubMedDate not supplied

Group B streptococcus in the perinatal period. A review.

Prior to the 1960s, little was known about morbidity and mortality in humans due to group B streptococcus (GBS). Since that time, a thorough understanding of the organism's potential has been developed. Of pregnant women, 20-30% are prenatal carriers of GBS and 40-75% of these mothers will transmit GBS to their neonates. However, the actual incidence of GBS disease in infants is one to three cases per 1,000 live births. Several risk factors for transmission and development of early-onset GBS disease have been identified. The understanding of late-onset disease is less clear. Many strategies have been investigated to find an optimal protocol to reduce significantly the incidence of GBS disease in a cost-effective manner. The Centers for Disease Control and Prevention have recently made recommendations for prevention strategies against this disease.

Antibiotic Prophylaxis↗

PubMed1998

Sequential flow cytometry and fluorescence in situ hybridization for the study of formalin-fixed, paraffin-embedded breast cancer cells.

Both flow cytometry and fluorescence in situ hybridization (FISH) are useful techniques in the analysis of cancer tissues. When the two are used in the study of the same specimens, they are usually performed in parallel, separately. This is problematic where there is a scarcity of material, making completion of both studies impossible. Fluorescence in situ hybridization procedures that will utilize excess material discarded from flow cytometry would be advantageous. The present report describes an optimized protocol for performing sequential flow cytometry and FISH using formalin-fixed paraffin-embedded archival material. Although breast cancer tissues were used in this initial study, the protocol is applicable to other cancer tissues as well.

Breast Neoplasms↗

PubMed1999

Trisomy 8 in embryonal rhabdomyosarcoma detected by fluorescence in situ hybridization.

Embryonal rhabdomyosarcoma is the most common malignant soft-tissue tumor in childhood. Cytogenetic studies of this tumor are rare. In one study trisomy 8 was found to be a primary cytogenetic abnormality. In view of the findings of trisomy 8 in a multitude of cancers, we conducted a pilot study to test the hypothesis that a subset of rhabdomyosarcoma also exists with trisomy 8. Accordingly, archival tissues of 12 cases of rhabdomyosarcoma were retrieved and fluorescence in situ hybridization (FISH) using a chromosome 8-specific, alpha-satellite probe was undertaken on formalin-fixed paraffin-embedded tissue sections using the protocol optimized in the Cytogenetics Laboratory at Rhode Island Hospital. The results obtained demonstrated that 6 of 12 tumors showed chromosome 8 trisomy, when a 15% threshold is adopted. In addition, one case was borderline, with 11% of the cells found positive for three fluorescent signals. Future experiments utilizing additional specimens from our centers as well as from other laboratories are needed to confirm and extend the findings of the present study.

Cell Differentiation↗

PubMed1998

Ligand-binding studies: old beliefs and new strategies.

Ligand-binding studies remain a very popular technique among many experimentalists. As far as equilibrium experiments are concerned, saturation and displacement curves are commonly performed for simplicity, convenience or for the sake of tradition. However, alternative protocols, such as 'mixed'-type protocols or multiligand experiments, are also possible. Indeed, there are cases where kinetic experiments, usually considered a 'second-choice' experiment, might have a superior resolving power compared to equilibrium ones. A combination of equilibrium and kinetic experiments might be a powerful solution to overcome limits and shortcomings of each specific technique and is discussed in this issue by G. Enrico Rovati. Thus, a careful choice of the design, a protocol optimization and a computerized analysis of the data can yield a dramatic improvement in the precision of the parameter estimation over more conventional approaches.

Computer Simulation↗