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PubMed1979

[Progress and developments in insulin therapy].

BANTING and BEST revolutionized diabetes therapy with the discovery of insulin 57 years ago. Since then, progress in this area has been slow despite tremendous reseach efforts. The subcutaneous injection of a depot insulin does not provide optimal control of blood sugar. True progress has been brought about by intravenous insulin administration for the management of diabetic coma. The authors do not recommend ultra low dose therapy. The prognosis of diabetic coma is much better than 20 years ago, in particular because of much improved and continuous supervision of the circulation (CVP, ECG, K+ etc.). Pancreas and islet transplantation fail in man due to immunological rejection. The "artificial pancreas" with a glucose sensor is useful for research purposes, and for controlling blood sugar for a few days at most. The implantable glucose sensor is not yet in sight. The authors have treated diabetics successfully with a programmable flexible open loop infusion program. The basal insulin infusion rate can be varied from 0.25 to 2 U/h, and rectangular one hour extra insulin infusions between 2 and 10 U/h are superimposed by pushing a button on the steering unit. The pump automatically switches back to the basal rate after one hour. No hypoglycemic reactions have been observed in patients on ths program on the ward or at home. At present, technical problems with the catheter remain to be solved before this simple therapeutic approach can be applied routinely.

Adolescent↗
PubMed1979

Optimal blood sugar control in labile diabetics using a portable open-loop insulin infusion system with a flexible program.

11 labile diabetics were well controlled after 2 days of an i.v., open-loop insulin infusion program consisting of constant, empirically determined, basal infusion rates (mean: 1.1 U/h) and superimposed rectangular one-hour insulin infusions between 2 and 8 U/h during the main meals. The steering unit switches automatically back to the basal infusion rate after one hour. An almost optimal blood sugar profile was already obtained on the third day of the infusion program. We believe that such a flexible, open-loop insulin infusion program would render long-term optimal blood sugar control in "labile" diabetics possible if the technological development ever allows implantation of the infusion pumps.

Adolescent↗
PubMed1978

The hypercalciuria of diabetes mellitus: its amelioration with insulin.

Calcium and phosphous metabolism was investigated in 20 patients with diabetes mellitus when their diabetes was under poor metabolic control and again once optimal glycaemic control was achieved with aggressive insulin therapy. Ten of the twenty uncontrolled diabetics had hypercalciuria; insulin therapy returned calcium excretion to normal in five. Twenty-four hour calcium excretion fell in all but two patients when optimal diabetic control was achieved and calcium excretion was positively correlated with glucose excretion. Urinary cyclic AMP excretion, which was in the high normal range during poor control, decreased significantly during optimal insulin therapy. These data suggest that the hypercalciuria of uncontrolled diabetes may be a form of renal hypercalciuria which could result in parathyroid stimulation which might contribute to the development of osteopenia in patients with diabetes mellitus.

Adult↗
PubMed2026

Technology choice, glycemic control and patient-reported outcome measures in adults with type 1 diabetes: A randomized crossover trial comparing a smart insulin pen with an automated insulin delivery system (EBIACE-1).

AIMS: To compare glycemic outcomes and patient-reported outcome measures (PROMs) between smart insulin pens (SIP) and an automated insulin delivery (AID) system in adults with type 1 diabetes (T1D), and to identify individuals able to maintain near-optimal glycemic control using SIP. METHODS: EBIACE-1 was a randomized, open-label, crossover trial including 31 adults with T1D. Participants received SIP (InPen&#x2122;) and AID (MiniMed&#x2122; 780G) for 6&#xa0;months each. Co-primary outcomes were time in range (TIR 70-180 mg/dL) and HbA1c. Treatment effects were assessed using longitudinal models in intention-to-treat (ITT) and per-protocol (PP) analyses. Predictors of near-optimal glycemic control with SIP were evaluated using multivariable logistic regression. RESULTS: AID improved glycemic control versus SIP, with higher TIR (81&#xa0;% vs 66&#xa0;%; +15&#xa0;%, 95&#xa0;% CI 10-19; P&#xa0;<&#xa0;0.001) and lower HbA1c (6.9&#xa0;% [52&#xa0;mmol/mol] vs 7.3&#xa0;% [56&#xa0;mmol/mol]; -0.4&#xa0;%, 95&#xa0;% CI&#xa0;-&#xa0;0.6 to&#xa0;-&#xa0;0.3; P&#xa0;<&#xa0;0.001). Near-optimal glycemic control with SIP was achieved by 12 of 26 participants (46&#xa0;%). In exploratory analyses, higher baseline diabetes-related life interference was associated with a lower probability of achieving this outcome. CONCLUSIONS: AID provides superior glycemic control, although nearly half of participants achieved near-optimal control with SIP, supporting a personalized approach to technology selection.

Adult↗
PubMed1978

Osseous repair in infrabony periodontal defects.

The present investigation was undertaken to quantitate the osseous changes which occur throughout the entire circumferential extent of infrabony periodontal defects in patients with optimal plaque control. Fifteen defects were selected in nine patients. Periodontal surgery was scheduled after each patient had shown an ability to practice efficient plaque removal. Muco-periosteal flaps were raised and the osseous defects debrided. The dimensions of each defect were measured at several specific location points within the defect. The flaps were replaced at their original location and, post-operatively, optimal plaque control was maintained in the area (Mean Plaque Index 0.04). Six to 8 months after the initial surgery all areas were re-operated and the osseous defects were remeasured at the same specific location points. Each defect showed osseous regeneration at every location point. The mean initial osseous defect depth at a location point was 3.5 mm and the mean amount of bone regeneration which occurred was 2.5 mm. Crestal alveolar bone resorption occurred at almost half of the location points and averaged 0.7 mm. Eleven of the 15 defects had resolved completely. There were isolated areas where a shallow defect persisted in the remaining four defects. The behavior of an osseous defect throughout its circumferential extent was characterized by a combination of coronal bone regeneration (mean 77%) and marginal bone resorption (mean 18%). Infrabony periodontal defects may predictably remodel after surgical debridement and establishment of optimal plaque control.

Adult↗
PubMed1978

High Rates of controlled ultrafiltration combined with optimal diffusion: recent advances in hemodialysis technique.

A system which permits high rates of middle molecule removal while preserving the removal of low molecular weight substances is described. It consists of a high fluid flux hollow fiber artificial kidney and an ultrafiltration controller. When used in combination, high rates of convective transport can be achieved through rapid ultrafiltration and reconstitution of blood with physiologic salt solutions. The theoretical impact of changing from conventional dialysis to this form of therapy on the body burden of middle molecules is estimated.

Diffusion↗
PubMed1977

[The effect of metabolic control on the development of late complications of diabetes (author's transl)].

The fate of the diabetic today is essentially determined by the late complications of diabetes. Of the forms of clinical expression of diabetic microangiopathy, nephropathy and retinopathy are the most significant. Findings are presented which suggest that diabetic microangiopathy is not of genetic or immunologic origin, but is to be considered a consequence of insulin deficiency. More recently, some studies have been carried out which which strongly support the concept that metabolic control of the diabetic prevents or at least delays the development of late complications of diabetes. For this reason an optimal for control of diabetes, if at all possible with aglycosuria, should be aimed at.

Animals↗
PubMed2026

Design and optimization of a kinase-controlled allosteric switch.

Post-translational control enables rapid and precise regulation of cell behavior. Despite these advantages, general strategies to build phosphorylation-based synthetic circuits are limited. Here we reasoned that engineered allostery, a technique that has been applied to design light- and chemically gated protein switches, could also be used to engineer phosphorylation-controlled protein switches (phospho-switches). Using an allosterically controllable Gal4 transcription factor as a scaffold, we show that a classic kinase F&#xf6;rster resonance energy transfer biosensor architecture can be used as a starting point for phospho-switch design. We optimize all features of the phospho-switch to develop an ERK-controlled transcription factor with a 20-fold phosphorylation-dependent change in transcriptional output. The resulting synthetic ERK-responsive transcription factor responds with comparable sensitivity to the c-fos promoter and reveals spatial ERK signaling patterns in mammalian developmental organoids. We further show that our switch architecture can be generalized to other input kinases and allosterically controlled targets. This work provides a general platform for a new generation of kinase-responsive tools for biosensing and synthetic biology applications.

Allosteric Regulation↗
PubMed1979

Therapeutical application of artificial beta-cell in surgery and obstetrics.

An artificial beta-cell (Biostator) was used to control blood glucose concentration in six insulin-dependent diabetics who underwent surgical procedures and in five diabetic women during both vaginal childbirth and Caesarian section. In all cases, an optimal glycometabolic control was achieved before, during, and after surgery and delivery.

Adult↗
PubMed1979

The dose-time relationship in the radiotherapy of carcinoma of the cervix uteri: an application of the CRE formalism.

A correlation could be obtained between the likelihood of control of central and nodal disease and the corresponding local CRE levels attained in a group of 79 cases of carcinoma of the cervix uteri treated according to a multistage protocol involving a combination of external telecobalt irradiation and intracavitary radium application. A nodal CRE level of 1700 reu and a central CRE value of 2900 reu seemed to be optimal for control of modal metastases and central disease respectively. These CRE levels seemed to be well tolerated even if salvage surgery had to be performed.

Carcinoma, Squamous Cell↗
PubMed1979

1 alpha-Hydroxycholecalciferol and calcium deficiency osteoporosis in adult rats.

An attempt was made to reverse the osteoporotic changes caused by calcium deficiency in adult male rats, partly by a daily oral administration of 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) over a period of 6 weeks, partly by additionally changing to an optimal calcium intake during the same period of treatment. The results achieved show that 1 alpha-OH-D3 combined with an optimal calcium-containing diet significantly normalized the skeleton when compared with low or optimal calcium controls. 1 alpha-OH-D3 in combination with a contiuous intake of low calcium could not significantly restore these changes during the observation time. The bone matrix composition of collagen, glycosaminoglycans and nucleic acids did not change significantly during treatment. However, new bone formation as measured by uptake of fluoretic material was noted to increase pari passu with treatment with 1 alpha-OH-D3, combined either with an optimal or with a low calcium intake. The evidence of direct and/or indirect effects of 1 alpha-OH-D3 on the new bone formation is discussed.

Administration, Oral↗
PubMed1979

[Efficiency of cancer-preventive examinations. Problems in early detection for the physician and laboratory].

The efficiency of gynecological cancer detection and verification depends on optimal team work of different medical specialties, such as General Medicine, Gynecology, Cytopathology, Histopathology, Surgery, Radiology. Each number of the team, working incompetently in its field, lowers the efficiency of the whole group. The most important factors leading to inefficiency in gynecological cancer detection and verification are discussed. The comparison of two different sized cancer detection programs (1962-1964; 38 119 patients vs. 1968--1976: 331 355 patients) revealed that the efficiency of verification of cancer cases does not improve with the size of the program: The cancer verification rates were higher in the small program with less routine work-up material (verification rate: 80%) compared withe the big program containing mostly follow-up cases (verification rate:75%). Much more attention should be paid to the control of optimal cooperation of the medical specialties participating in a cancer detection program, since not only the size of a program but the quality of the work-up can improve the results in cancer detection.

Family Practice↗
PubMed2026

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans↗
PubMed2026

Integrating genomics, multi-omics, CRISPR and speed breeding for stress-resilient vegetable legume improvement.

Vegetable legumes are nutritionally and ecologically important crops. However, their genetic improvement has not kept pace with the increasing challenges posed by climate change due to the polygenic nature of stress tolerance, narrow genetic diversity, and the persistent gap between molecular discoveries and field-level cultivar development. Although recent reviews have examined individual genomic tools or specific stress responses, a comprehensive synthesis integrating genomics-assisted breeding, multi-omics technologies, genome editing, and speed breeding within a unified crop improvement framework has been lacking. This review addresses that gap by critically evaluating how these complementary approaches can accelerate the development of stress-resilient vegetable legumes, including pea, common bean, cowpea, faba bean, cluster bean, yard-long bean, and hyacinth bean. This review synthesizes advances in QTL mapping, genome-wide association studies, transcriptomics, metabolomics, and CRISPR-based functional genomics that have identified key regulators and pathways underlying resistance to major biotic and abiotic stresses. Rather than considering these technologies independently, the review emphasizes their convergence into a systems-level breeding framework integrating genomic discovery, functional validation, predictive breeding, and accelerated generation advancement to improve breeding efficiency. Speed breeding, enabling up to seven to eight generations annually under optimized controlled-environment experimental conditions in cowpea, is discussed as a complementary strategy with genomic selection and genome editing. The review further identifies major translational bottlenecks, including transformation recalcitrance, limited genomic resources for underutilized vegetable legumes, inadequate multi-environment validation, and fragmented omics integration, and presents an integrated systems-breeding framework to bridge the gap between gene discovery and cultivar development.

Fabaceae↗
PubMed2026

From Variability to Consensus: Rescoring Harmonizes Peptide Identification across Diverse Search Engines and Data Sets.

Peptide-spectrum match (PSM) rescoring has become standard in proteomics workflows, improving peptide identification accuracy across diverse search engines. Despite the availability of multiple rescoring strategies, systematic comparisons spanning several search engines, data sets, and database configurations remain limited. Here, we benchmarked seven publicly available search engines, evaluating standard target-decoy-based false discovery rate (FDR) estimation alongside Percolator, MS2Rescore, and Oktoberfest across four data sets acquired on different mass spectrometry platforms in data-dependent mode and searched against protein databases of varying size and composition. Rescoring substantially increased identification consensus and reduced variability between search engines, with prediction-based approaches yielding the largest gains. While database size had limited impact for human data sets, it significantly affected identification rates on a metaproteomic data set. Entrapment-based evaluation indicated generally adequate FDR control across methods, although prediction-based rescoring exhibited a higher tendency toward FDR underestimation in specific configurations. Overall, advanced rescoring strategies harmonize peptide identification outcomes across search engines, thereby enhancing robustness and comparability in proteomics analyses. However, careful feature selection and appropriate database choice remain essential to ensure reliable FDR control and optimal performance across diverse experimental settings.

Search Engine↗
PubMed1979

Aging in the rhesus monkey: effects on visual discrimination learning and reversal learning.

The behavior of aged rhesus monkeys (18 years and older) was compared to that of young monkeys (3 to 6 years old) to evaluate their relative abilities to learn a series of visual discrimination and discrimination reversal problems. Using a subject-paced, automated experimental procedure designed to optimize stimulus control and facilitate execution of choice responses, no consistent age-related differences were observed in the ability to learn new color and pattern discrimination problems of varying difficulty. However, a severe and consistent deficity on reversal learning did occur. A detailed analysis of this deficit revealed that not only did the aged monkeys take longer to extinguish the old habit and return to chance performance, but they continued to display a deficit in establishing accurate performance at above-chance levels as well. Since no reliable age differences were observed on the original discrimination learning problems, these data suggest that aging impairs mechanisms involved with response rigidity and/or susceptibility to intertrial proactive interference, more severely than those involved with the simple formation of new associations.

Aging↗