Cholecystokinin (CCK) is a hormone secreted by the I-cells of the upper small intestine in response to fat, protein, and some nonnutrients, for example, camostat, and a peptide/neurotransmitter ...secreted by neurons of the central and peripheral nervous systems. There are multiple molecular forms of CCK, for example, CCK-8, CCK-33, and CCK-58, with an active site located within the first eight amino acids of the carboxyl terminus and with a sulfate group on the seventh tyrosine residue. Physiologically, CCK increases pancreatic secretions and gallbladder and smooth muscle contractions as well as inhibits gastric emptying and food intake. CCK evokes these responses by activating two G protein-coupled receptors: CCK(1) and CCK(2). CCK(1) receptors are located mainly in the alimentary tract and contain two affinity states, high and low, whereas CCK(2) receptors are found mainly in the brain. Although a CCK-mediated reduction in cumulative food intake occurs by the activation of low-affinity CCK(1) receptors located on vagal afferents, the vagus, and the splanchnic nerves are necessary for the reduction of meal size (MS) and the prolongation of the inter-meal interval (IMI) by CCK. Finally, the reduction of food intake by CCK occurs by three possible modes of action: paracrine, endocrine, and neurocrine; thus far, the data favor a paracrine mode. In addition, the gut, which is the main source of peripheral CCK, contains the first neuronal component that senses the presence of food, the enteric nervous system. The enteric nervous system may have a role in the reduction of MS and the prolongation of the IMI by CCK.
In 2005, the high power thulium laser was introduced for the surgical treatment of benign prostatic obstruction. It has several properties that confer theoretical advantages over other lasers used ...for the same indication, such as technical versatility and a relatively small zone of thermal damage. Studies using the 70–150 W thulium laser systems demonstrate good efficacy of these procedures with low morbidity and few complications even in higher risk patients. Different techniques have been employed to treat the prostate with this technology, including enucleation, vapoenucleation, vaporization and resection. Comparative studies have been published comparing thulium laser prostatectomy to monopolar transurethral resection of prostate (TURP), bipolar TURP and holmium laser enucleation of prostate (HoLEP). In this review we discuss the current literature on the safety and efficacy of various thulium techniques for the treatment of benign prostatic hyperplasia and examine comparative studies.
The current study measured seven feeding responses by non-sulfated cholecystokinin-8 (NS CCK-8) in freely fed adult male Sprague Dawley rats. The peptide (0, 0.5, 1, 3, 5 and 10 nmol/kg) was given ...intraperitoneally (ip) prior to the onset of the dark cycle, and first meal size (MS), second meal size, intermeal interval (IMI) length, satiety ratio (SR = IMI/MS), latency to first meal, duration of first meal, number of meals and 24-hour food intake were measured. We found that NS CCK-8 (0.5 and 1.0 nmol/kg) reduced MS, prolonged IMI length and increased SR during the dark cycle. Furthermore, the specific CCK-B receptor antagonist L365, 260 (1 mg/kg, ip) attenuated these responses. These results support a possible role for NS CCK-8 in regulating food intake.
•NS CCK-8 reduces food intake in adult rats.•NS CCK-8 prolongs the intermeal interval.•NS CCK-8 increases the satiety ratio.•reduction of food intake by NS CCK-8 occurs through CCK B receptor.•NS CCK-8 may have a role in control of food intake.
Abstract Study question Can an AI-based embryo ploidy screening tool effectively provide a genetic risk assessment on Day 5 embryos? Summary answer AI screening results showed strong predictive value ...for early detection of at-risk embryos warranting confirmatory diagnostic testing, based only on time lapse video assessment. What is known already Euploid embryo transfer is the dogma of IVF success. Embryo evaluation relies extensively on diagnostic preimplantation genetic testing for aneuploidy (PGT-A) by means of trophectoderm biopsy. Though pivotal, this presents substantial practical and financial limitations. There is demand for an alternative genetic screening method that provides a quantitative embryo genetic risk assessment for patients who opt out of invasive diagnostic testing, or who intend to undergo fresh transfer. These results can provide information for understanding your aneuploidy risk for more precise prognosis counseling and testing. This is important since diagnostic tests may incur excess financial burden, inconclusive outcomes, and time-to-results. Study design, size, duration Time lapse videos (N = 5,000) were used for AI training. The AI core architecture was a video transformer model for spatio-temporal video sampling. Known ploidy and live-birth results were used as ground truth, with maternal age and embryo quality scores incorporated as input parameters during calibrated logistic regression. A blind test dataset (N = 708 embryos; euploid=352; aneuploid=356; mean ± SD patient age: 35.9 ± 5.4 years) was used to evaluate predictive accuracy. Participants/materials, setting, methods The AI outputs a scalar (1-99) that associates with euploidy likelihood. The AI’s screening value was determined by its specificity (correct prediction of aneuploid), sensitivity (correct prediction of euploid), false positive, and false negative rate. We determined optimal AI score thresholds that identified high aneuploidy and euploidy risk categories (AI score <33; AI score >66, respectively). Main results and the role of chance Specificity of the AI screening test was 83.0%, with a sensitivity of 56.0%. The false positive rate was 26.7% and the false negative rate was 29.3%. The AI’s high specificity relative to its sensitivity shows its clinical value to deselect embryos with the strongest risk of genetic abnormality, and for the prioritization of embryos for confirmatory PGT. Boxplot visualization of the full AI score distribution showed successful discrimination between aneuploid and euploid embryos (mean AI score for aneuploid and euploid were 51.3 and 43.5, respectively) with appropriately minimized overlapping of the interquartile range. The optimal AI score thresholds for detecting embryos with the highest and lowest likelihoods of euploidy were >66 /<33, respectively, representing 71% likelihood of euploidy for the >66 group and 72% aneuploidy for the <33 group. Limitations, reasons for caution The screening does not provide diagnostic genetic testing on the chromosome level. The influence of mosaicism on the false positive/negative rates was not assessed. Wider implications of the findings Results support the use of an AI ploidy screening test for effective decision-making and triage of at-risk embryos for transfer or confirmatory diagnostic testing via PGT-A. Trial registration number Not applicable
Abstract Study question Can calibrated AI ploidy screening test results provide reliable, biologically-justified estimates of embryo euploidy? Summary answer The AI ploidy screening test, rooted in ...the embryo’s morphokinetic profile and clinical metadata, provides reliable probabilistic estimates of euploidy. What is known already Published ploidy algorithms typically provide a binary classification of embryo ploidy (aneuploidy/euploidy). Algorithmic outputs are thresholded; a value above/below the threshold indicates a euploid/aneuploid label, respectively, and the confidence in the label prediction is tested. Experience shows, however, that decision-makers have difficulty interpreting how well these algorithm predictions match the true prevalence of euploidy in their clinics, especially when taking into consideration patient age and embryo quality. An AI embryo ploidy screening tool that uses biologically-relevant inputs to provide reliable euploidy probabilities is needed. Study design, size, duration The AI tool was trained on 5,000 time-lapse video sequences, along with associated clinical parameters: biological age at time of retrieval, Day-5 embryo quality, and morphokinetic parameters ranging from time of pronuclear fading to time to blastulation. Probability calibration was applied and its performance was evaluated using a blind test dataset (N = 708 embryos; euploid=352; aneuploid=356) with known prevalences of euploidy, aneuploidy, and live-birth. Mean ± SD patient age: 35.9 ± 5.4 years. Participants/materials, setting, methods The AI ploidy screening tool used known embryo ploidy status as ground-truth labels; biological age and visual quality parameters were incorporated as continuous input features to maintain biological validity. Reliability curve analysis, which plots the observed frequencies of euploidy in the clinical input data (y-axis) against the predicted probability frequencies by the screening test (x-axis), was used to assess model confidence. Odds ratios (OR) confirmed significance between associations. Main results and the role of chance Logistic regression analysis shows that AI scores are robustly associated with euploidy probability (OR = 2.79 95% CI = 2.04-3.81 at a threshold of 0.5 when comparing euploid likelihood for high-versus-low AI scores). For embryo cohorts in the blind test set containing ≥1 aneuploid and euploid embryos in the test dataset, (N = 57 cohorts), the highest AI ranked embryo was euploid in 64% of the cohorts. Embryos were divided into four predefined brackets according to their scores (1-32, 33-49, 50-66, 67-99) and euploidy rate per bracket was determined: 28%, 44%, 58%, 71%, respectively. There was a linear association between ascending AI scores and percentage of euploid embryos, with the highest level of model confidence achieved at the tail ends of the scalar; embryos with a score above 66 were 2.5X more likely to be euploid than an embryo with a score below 33. Limitations, reasons for caution This analysis used historical time-lapse sequences. Moving forward, we must evaluate prospective AI use for ploidy screening. Genetic status in utero/birth was not evaluated. Wider implications of the findings A novel AI approach for preimplantation embryo screening using clinical metadata and time-lapse videos can improve our ability to non-invasively predict euploid likelihood prior to confirmatory diagnostic preimplantation genetic testing. Trial registration number Not applicable
This study develops a method to determine toricity ratios used by arbitrary toric intraocular lens calculators. Access to this information allows for the improvement of refractive results. We derive ...the Sayegh-Gabra formula, which uses input and output parameters in a toric calculator to extract toricity ratios that are typically not disclosed. We illustrate the method on a number of commercial calculators. For each calculator, high, average, and low axial length values are crossed with high, average, and low mean corneal power values to generate a 3 × 3 matrix. A toricity ratio is generated for each axial length and mean corneal power pair. We thus identify several toric lens manufacturers' calculators that use a constant toricity ratio, often 1.46. Some others use a variable ratio centered at 1.46, but varying as axial length and mean K increases over a range of values corresponding to physiological myopia and hyperopia. There is an emerging trend away from constant toricity ratios. Using our methodology, it is possible to extract the toricity ratio used by specific calculators/manufacturers, distinguish those using constant versus variable toricity ratios, and use this information to improve surgical outcomes by refining current and future toric intraocular lens calculators.
•Non-sulfated cholecystokinin-8 (NS CCK-8) reduced food intake.•NS CCK-8 increased Fos-LI immunoreactivity (Fos-LI) in the hindbrain.•NS CCK-8 increased Fos-LI in the myenteric neurons.•NS CCK-8 ...increased Fos-LI in the submucosal neurons.•These neurons may have a role in reduction of food intake by NS CCK-8.
Recently, we reported that non-sulfated cholecystokinin-8 (NS CCK-8) reduces food intake by cholecystokinin-B receptors (CCK-BR). To examine a possible site of action for this peptide, and based on the fact that both NS CCK-8 and CCK-BR are found centrally and peripherally, in the current study we hypothesized that NS CCK-8 increases Fos-like immunoreactivity (Fos-LI, a neuronal activation marker) in the dorsal vagal complex (DVC) of the hindbrain and the myenteric and submucosal plexuses of the small intestine. We found that intraperitoneal NS CCK-8 (0.5 nmol/kg) increases Fos-LI in the DVC, the myenteric and the submucosal plexuses of the duodenum and the myenteric plexus of the jejunum. The findings suggest, but does not prove, a potential role for the DVC and the enteric neurons in the feeding responses evoked by NS CCK-8.
Two separate experiments were performed to localize the gastrointestinal sites of action regulating meal size (MS), intermeal interval (IMI) length and satiety ratio (SR, IMI/MS) by cholecystokinin ...(CCK) 8 and 33. Experiment 1: CCK-8 (0, 0.05, 0.15, 0.25nmol/kg) was infused in the celiac artery (CA, supplies stomach and upper duodenum) or the cranial mesenteric artery (CMA, supplies small and part of the large intestine) prior to the onset of the dark cycle in free feeding, male Sprague Dawley rats and MS (normal rat chow), IMI and SR were recorded. Experiment 2: CCK-33 (0, 0.05, 0.15, 0.25nmol/kg) were infused in the CA or the CMA, under the same experimental conditions above, and MS, IMI and SR were recorded. Experiment 1 found that CCK-8 reduces MS, prolongs the IMI and increases the SR at sites supplied by both arteries. Experiment 2 found that CCK-33 reduces MS and increases the SR at sites supplied by the CMA. We conclude that in male rats the feeding behaviors evoked by CCK-33, but not CCK-8, are regulated at specific gastrointestinal sites of action.
•Cholecystokinin (CCK) -8 infused in the Celiac Artery (CA) reduced meal size (MS)•CCK-8 infused in the CA prolonged the intermeal interval (IMI) and increased satiety ratio (SR)•CCK-8 infused in the Cranial Mesenteric Artery (CMA) reduced MS, prolonged the IMI and increased the SR•CCK-33 infused in the CMA reduced MS and increased SR•CCK-33, but not CCK-8, is regulated by specific sites in the gut
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