[Treatment sequence for drug addicts].
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Humans↗
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Graded group procedures for long term regressed schizophrenics.
It has been suggested that a graded sequence of treatments might be the most efficacious approach to the rehabilitation of the regressed schizophrenic. To date, however, no research has been reported which examines the relative effectiveness of various treatment combinations with this difficult population. The present study is an investigation of the relative effectiveness of three treatment sequences in increasing social interaction among long term regressed schizophrenics. In this study, 32 chronic schizophrenic patients were randomly assigned to one of three treatment sequences or to a control group. Each sequence began with six sessions of remotivation group therapy. Following, this, one group participated in four sessions of activities, another had social living discussions, and a third continued with remotivation therapy. Both the remotivation-activities sequence and the remotivation-only sesequence significantly increased social interaction relative to the remotivation-social living sequence and thecontrol group. Therefore it appears that both the activities groups and the remotivation groups are effective early components of a graded treatment program to increase social interaction among withdrawn schizophrenics.
Adult↗
Effects of a marriage enrichment program: an outcome study.
This study investigated the impact of a marriage enrichment program. Fourteen couples were randomly assigned to one of two experimental groups or to a no-treatment control group. One experimental group received fair-fight training for 3 weeks followed by a sexual enhancement format for 3 additional weeks. The second experimental groups received the opposite treatment sequence. The same counselor team used the same exercises in both groups. The sequence of treatment did not differentially affect outcome. The immediate and longer term treatment effects that were found generally favored the treatment groups over the no-treatment control group on spouses' separate reports of marital and personal functioning. Using larger and more homogeneous samples, future studies should examine the relationship of individual partner changes to couple changes, conduct a follow-up evaluation of at least 3 months, and obtain behavioral assessments of couples' interactions before and after treatment.
Aggression↗
Short-term effects of different toothpaste formulations on total salivary calcium: A randomized crossover study.
OBJECTIVES: Dental calculus formation can be inhibited by toothpastes containing pyrophosphate, which chelates calcium ions and prevents hydroxyapatite crystal formation. Although pyrophosphate may also influence salivary calcium availability, the short-term effects of commercially available toothpaste formulations on salivary calcium concentrations remain insufficiently characterized. This study investigated and compared the short-term effects of three fluoride toothpastes on salivary calcium concentration. METHODS: A randomized, three-treatment, three-period crossover trial was conducted in 48 healthy volunteers. The participants used three commercially available sodium fluoride toothpastes in randomized order: a formulation containing methyl vinyl ether/maleic acid copolymer, PVM/MA copolymer (Sensodyne), a formulation containing pyrophosphate and zinc (Dentalux), and a formulation containing sodium bicarbonate (Parodontax). Treatment periods were separated by a 2-day washout. Unstimulated saliva was collected at baseline (T0), immediately after brushing (T1), 30 min (T2), and 60 min (T3). Salivary calcium concentrations were quantified using a colorimetric assay. Data were analysed using linear mixed-effects models with toothpaste formulation, measurement time, treatment sequence, and the toothpaste-by-time interaction as fixed effects and participant as a random effect. RESULTS: Significant effects were observed for toothpaste formulation (F(2,103.35)=42.31, P < 0.001), measurement time (F(3,141)=39.78, P < 0.001), and the toothpaste-by-time interaction (F(6,141)=23.91, P < 0.001), whereas treatment sequence had no significant effect (P = 0.927). Compared with Dentalux® and Sensodyne®, Parodontax® resulted in significantly lower salivary calcium concentrations (both Bonferroni-adjusted P < 0.001), immediately after brushing (T1). The differences decreased after 30 min and were no longer significant after 60 min. No significant differences were observed between Dentalux® and Sensodyne® at any time point. CONCLUSIONS: Commercially available fluoride toothpastes produced different short-term effects on the salivary calcium concentration, with the greatest differences occurring immediately after brushing. Because the products differed in terms of multiple formulation ingredients, the findings reflect product-level effects rather than ingredient-specific effects. Further multicentre studies are warranted to confirm these findings and evaluate their clinical relevance.
Humans↗
Radiology at war.
It can be assumed that the high percentage of wounded sent immediately from the triage area to the department of radiology was a reflection of the necessity for X-rays. The radiological examination was essential in reaching the correct diagnosis, and the radiologist was the central consultant, as by giving the diagnostic information and performing therapeutic angiographic intervention, he actively participated in the treatment of the patient. The radiologist and the surgeon together reached the final decision as to which injury prevailed and in which sequence treatment had to be planned. Hence, the department of radiology became the vital link in flow of patients from the sorting area to the operating theatre.
Abdominal Injuries↗
The effect of Waring Blendor treatment on transformation in Bacillus subtilis.
Treatment of competent Bacillus subtilis in a Waring Blendor for 10 s increases transformability of the culture about twofold while reducing the attachment of DNA to competent cells by 80%. The effectiveness of attached DNA in producing transformants is increased 10-fold by this treatment. The uptake of transforming DNA into a DNase-resistant state is progressively reduced by 70% during a 120-s blending treatment. Blending for 30-45 s diminishes transformability to about 10% of the original nonblended value without affecting the viable cell titer. No effect is produced by 30 s of blending on transformability if the irreversible uptake of DNA has been completed. Thus, the inhibition occurs at an early step in the transformation sequence. Treatment of the competent culture for 60 s or longer in the Waring Blendor reduces both the number of transformants obtained and the total number of viable cells.
Bacillus subtilis↗
How Have Massively Parallel Sequencing Technologies Furthered Our Understanding of Oncogenesis and Cancer Progression?
Massively parallel sequencing technologies have been a boon to many fields of biological science, including oncology. Cancer is an umbrella term for many diseases featuring abnormal cellular growth due to genetic and epigenetic aberrations. Advances in sequencing technology allow for interrogation of the DNA and RNA of cancer cells and other cells in the tumor microenvironment down to a single-base resolution. However, these strides come after a rich history of ground-breaking biological assays, like the discovery of the Philadelphia chromosome in the context of leukemia. Many specific genetic and epigenetic modifications have been implicated in oncogenesis, cancer progression, and response to treatment. Sequencing technologies have also helped to associate populations of bacteria in the microbiome to cancer development and prognosis. However, all this new information, especially when procured via high-throughput methods, comes at the cost of being more computationally and staff-resource intensive. There is also more risk to the privacy of the individuals with sequenced genomes. Notwithstanding, the overall benefit of sequencing technologies can greatly outweigh the risks with careful advancements and continued focus on the goal: helping those affected by cancer via precision medicine. Cancer biology has been and will continue to be elucidated by sequencing innovations in ways unimaginable without it.
Humans↗
An Exosomal Signature for Preoperative Detection of Occult Liver Metastasis in Pancreatic Cancer.
IMPORTANCE: Early liver metastasis (early-LiM) after pancreatectomy represents an aggressive biological phenotype of pancreatic ductal adenocarcinoma (PDAC) and is associated with markedly poor survival. Reliable preoperative biomarkers to identify occult hepatic micrometastasis remain lacking. OBJECTIVE: To develop and externally validate a circulating exosomal microRNA (exo-miRNA)-based machine learning model for preoperative detection of occult early-LiM in PDAC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective case-control study included 3 phases: genome-wide discovery using exo-miRNA sequencing (discovery cohort), model development (training cohort), and independent external validation (2 validation cohorts). The study took place at 4 medical centers in China, Japan, and South Korea. A total of 372 patients were enrolled between 2011 and 2024. Data were analyzed from July 2024 to November 2025. EXPOSURES: Circulating plasma-derived exosomal miRNA expression profiles. MAIN OUTCOMES AND MEASURES: The primary outcome was early-LiM, defined as liver recurrence within 6 months after curative-intent resection. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and survival outcomes were assessed using Kaplan-Meier analysis. RESULTS: Among 372 patients with PDAC (median [IQR] age, 67 [59-73] years; 229 [61.6%] male and 143 [38.4%] female; median follow-up among survivors, 969 days),early-LiM was associated with significantly worse overall survival compared with other recurrence patterns (median OS, 9.1 months vs 26.6-31.8 months; log-rank P < .001). A 7-exo-miRNA extreme gradient boosting model demonstrated discrimination in the training cohort (AUC, 0.899; 95% CI, 0.822-0.976) and maintained performance in external testing cohorts (AUC, 0.876; 95% CI, 0.846-0.951 and AUC, 0.862; 95% CI, 0.744-0.981). The exo-miRNA panel score remained an independent identifier of early-LiM in multivariable analysis (odds ratio, 26.49; 95% CI, 18.45-55.28; P < .001) and stratified overall survival (log-rank P < .001). Decision curve analysis suggested improved net clinical benefit compared with conventional clinicopathologic variables. CONCLUSION AND RELEVANCE: In this multicenter study, a circulating exo-miRNA-based machine learning model enabled preoperative detection of occult early liver metastasis risk in PDAC. These findings support the potential of exosomal biomarkers to inform biology-guided treatment sequencing and warrant prospective validation.
Journal Article↗
Futibatinib after non-covalent FGFR inhibitors in FGFR2-rearranged intrahepatic cholangiocarcinoma: clinical activity and resistance patterns.
PURPOSE: The optimal sequencing of non-covalent and covalent FGFR inhibitors in FGFR2-rearranged intrahepatic cholangiocarcinoma (iCCA) remains undefined. Futibatinib, an irreversible FGFR1-4 inhibitor, may retain activity in the setting of acquired resistance to non-covalent FGFR inhibitors, but data on the patterns of acquired alterations are limited. METHODS: We conducted a retrospective multicenter study across three European centers including patients with advanced FGFR2-rearranged iCCA treated with futibatinib after progression on non-covalent FGFR inhibitors. Clinical outcomes and safety were evaluated. Available genomic profiling at progression was analyzed to characterize resistance mechanisms and their association with outcomes. RESULTS: Sixteen patients were included. Median progression-free survival (mPFS) with prior non-covalent FGFR inhibitors was 10.2 months (95% CI 7.0-15.5), with an objective response rate (ORR) of 60.0%. Among patients with post-progression genomic profiling (n = 11), all harbored FGFR2 resistance mutations, with polyclonal alterations (≥2) in 45.5%. A higher burden of FGFR2 mutations and the presence of co-alterations were associated with shorter mPFS on non-covalent inhibitors. Futibatinib was administered at a median of fourth-line therapy. ORR was 31.3% and disease control rate was 50.0%. Median PFS and overall survival were 4.5 months (95% CI 2.0-9.1) and 9.9 months (95% CI 5.7-not reached), respectively. Notably, outcomes with futibatinib were independent of the number of acquired FGFR2 resistance mutations, and the adverse impact of co-alterations appeared attenuated. Safety was consistent with the known profile. CONCLUSIONS: Futibatinib demonstrates clinically meaningful activity after progression on non-covalent FGFR inhibitors, supporting its use in FGFR2-rearranged iCCA, including in the post-non-covalent inhibitor setting. The distinct resistance patterns provide a biological rationale for the continued efficacy of covalent FGFR inhibition. Prospective studies incorporating longitudinal molecular profiling are needed to optimize treatment sequencing.
Drug resistance↗
The surgical-orthodontic correction of maxillary deficiency.
To date surgeons have primarily emphasized advancement of the retrusive or retodisplaced maxilla. There has been no emphasis on combined surgical-orthodontic treatment sequencing in this deformity. Moreover, the maxilla may be deficient not only anteroposteriorly but also vertically and/or transversely. Frequently, when the maxilla is deficient, two or three of these spatial components of the deformities coexist to various degrees. Thus, the term maxillary deficiency is used here to describe the general nature of the skeletal deformity.
Adolescent↗
Electron probe x-ray microanalysis of small granulated cells in rat sympathetic ganglia after sequential aldehyde and dichromate treatment.
Rat adrenal medulla and celiac-mesenteric sympathetic ganglia were fixed by a glutaraldehyde/formaldehyde-potassium dichromate-osmium treatment sequence and plastic-embedded. Fine sections were examined by electron probe x-ray microanalysis. Comparable peaks for chromium (Kalpha = 5.4 keV) were obtained from cytoplasmic fields containing membrane-bounded inclusion granules in both adrenomedullary noradrenaline cells and a type (type II) of sympathetic small granulated cell whose inclusion granules closely resemble those of the adrenomedullary noradrenaline cell. Chromium was not detected in granules within adrenomedullary adrenaline cells nor in two other sympathetic small granualted cell types. In no material was chromium detected in agranular cytoplasmic or nuclear fields. Since chromium binds to the Schiff monobase formed by glutaraldehyde and noradrenaline during fixation, we infer that noradrenaline is present in the granules of the type II sympathetic small granulated cell, as well as in adrenomedullary noradrenaline cells.
Adrenal Medulla↗
Comparison of sodium meclofenamate and indomethacin in rheumatoid arthritis.
A double-blind crossover study was conducted in 15 patients with classical definite rheumatoid arthritis to compare the effect of sodium meclofenamate (300 mg daily) with placebo and indomethacin (100 mg daily). Each treatment was administered for 1 week to patients assigned at random to treatment sequences. The active drugs were shown to be significantly superior to placebo. Sodium meclofenamate alone reduced the articular index. Patient preference, however, was in favour of indomethacin.
Adult↗
A double-blind, crossover trial of mefenamic acid, sulindac and flurbiprofen in rheumatoid arthritis.
A double-blind crossover trial was carried out in 24 patients to compare the effects of mefenamic acid, flurbiprofen, sulindac and placebo. Each drug was given for 2 weeks, the treatment sequence being randomized. Daily doses were 1500 mg mefenamic acid, 150 mg flurbiprofen or 150 mg sulindac. All of the active drugs were significantly superior to placebo in terms of pain score, patients' assessment, articular index of joint tenderness, and duration and severity of morning stiffness. There was improvement in grip strength compared with placebo, but the differences were not statistically significant with sulindac. There was slight reduction in joint circumference but this was only statistically significant in the right hand with flurbiprofen and sulindac. No significant differences were found in technetium uptake in knee joints. The three drugs appeared to be equally effective and tolerated, and no significant differences were noted.
Adult↗
The importance of histologic grade in stage II endometrial carcinoma.
Twenty-six patients with stage II endometrial carcinoma were reviewed. Survival time was found to be influenced most by histology. Fifteen of 19 patients with a favorable histologic grade survived. The combination of stage II disease and unfavorable histologic condition proved to be ominous, as there were no disease-free survivors in this group. Adequate combinations of pelvic irradiation and operation, as well as radiation therapy alone, provided satisfactory local control. Preoperative external irradiation and intracavitary insertion, followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy, are the preferred treatment sequence.
Adenocarcinoma↗
Recommendations for future research in hyperthermia at the molecular, cellular, and animal levels.
Recommendations are made for hyperthermia research to be carried out at the molecular, cellular, and animal levels. Effects of heat alone should be distinguished from effects of heat combined with radiation or chemotherapy. Factors to be considered include tumor cell environment, treatment sequencing, thermal tolerance, cell kinetics, any possible nonthermal effects, and therapeutic gain.
Animals↗
Sequencing and timing of treatment in the correction of dentofacial deformities in adult patients with clefts.
During the past six years, 107 patients with various dentofacial deformities secondary to primary clefts were treated in the cleft palate clinic. An overall treatment plan was formulated before any definitive secondary treatment was started. The sequencing and timing of the various aspects of secondary treatment were established to provide optimum esthetic, functional, and psychologic results.
Adolescent↗
A proper sequence for the treatment of B16 melanoma: chemotherapy, surgery, and immunotherapy.
The therapeutic effectiveness of surgery, chemotherapy, and immunotherapy alone and in combination were studied in the B16 melanoma model. The sequence of chemotherapy and immunotherapy as adjuvants to surgery proved important: Chemotherapy was significantly better when given before surgery; immunotherapy was more effective when delivered after surgery. The most effective therapeutic regimen was a combination of all three modalities: a single course of chemotherapy preceding surgery followed by immunotherapy.
Animals↗
Standardization for serial intraoral photography.
A recently developed system of mirror holders which makes the taking of standardized intraoral photographs less time consuming and more precise has been described. By fixing the relationship of the intraoral mirror to the camera, all that is necessary is to consistently orient the mirror to the teeth being photographed. Because the operator no longer has to position the mirror with one hand while holding the camera in the other hand, the whole operation of intraoral photography is greatly simplified. By producing serial slides of the progress of orthodontic treatment, a visual sequence of treatment can be prepared for viewing by patients, for educational purposes, and for showing at meetings and study clubs.
Dental Occlusion↗