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Lu, Z., T. R. Kolodecik, S. Karne, M. Nyce, and F. Gorelick. Effect of ligands that increase cAMP on caeruleininduced zymogen activation in pancreatic acini. Am J Physiol Gastrointest Liver Physiol 285: G822-G828, 2003. First published July 24, 2003; 10.1152/ajpgi.00213.2003.--The pathological activation of proteases within the pancreatic acinar cell is critical to initiating pancreatitis. Stimulation of acinar cells with supraphysiological concentrations of the CCK analog caerulein (CER) leads to protease activation and pancreatitis. Agents that sensitize the acinar cell to the effects of CCK might contribute to disease. The effects of physiological ligands that increase acinar cell cAMP [secretin, VIP, and pituitary adenylate cyclase activating peptide (PACAP)] on CER-induced responses were examined in isolated rat pancreatic acini. Each ligand sensitized the acinar cell to zymogen activation by physiological concentrations of CER (0.1 nM). VIP and PACAP but not secretin also enhanced activation by supraphysiological concentrations of CER (0.1 [micro]M). A cell-permeable cAMP analog also sensitized the acinar cell to CER-induced activation. The cAMP antagonist Rp-8-BrcAMP inhibited these sensitizing effects. These findings suggest that ligands that increase acinar cell cAMP levels can sensitize the acinar cell to the effects of CCK-induced zymogen activation. caerulein; chymotrypsin; secretin; trypsin

Aims & Objective: Obesity is a global health hazard and has been linked to numerous disorders including derangement in pulmonary functions and the negative association is still debated. This study is aimed at assessing the effects of obesity on slow vital capacity parameters. Materials and methods: A case control study was used to measure pulmonary parameters and was performed with a computerized spirolyser (with RS-232 connectivity). Slow vital capacity parameters measured between obese and non-obese groups were statistically analysed using student 't' test. Results: VC, ERV, IRV, IC and TV among obese were 2.78 ± 0.60, 0.59 ± 0.32, 1.70 ± 0.41, 2.27 ± 0.62 and 0.52 ± 0.23 in litre respectively. Same parameters among non-obese were 2.77 ± 0.61, 0.86 ± 0.37, 1.39 ± 0.53, 1.90 ± 0.47 and 0.53 ± 0.20 in litre respectively. Changes in ERV and IC was statistically highly significant ('p' <0.01), IRV was significant (<0.05) and VC, TV (>0.05) was insignificant (<0.05). Conclusion: Apart from IC and IRV, reduction in ERV was considered as the most significant and sensitive PFT parameters to know the negative association with class I (Mild) obesity. [ABSTRACT FROM AUTHOR]

Investigates intranasal heroin-induced hypersensitivity pneumonitis in a 25-year-old Hispanic woman with history of asthma. Pulmonary disease as an important complication of the use of cocaine and the intravenous use of heroin; High resolution computerized tomographic scan of the chest.

The acetabular triradiate cartilage is the main structure that determines the development of the acetabulum. Furthermore, the paucity of data in the literature and lack of consensus amongst physicians following diagnosis regarding whether to treat these fractures operatively or non-operatively places the physician with a challenging choice. Here, we report a case of a 13-year-old boy who suffered a triradiate cartilage fracture from a high-energy motorcycle crash and presented with a displaced, left T-type acetabulum fracture. The fracture was successfully treated surgically with open reduction and internal fixation (ORIF). At one year postoperatively, the patient has returned to daily activities, including noncontact sports, with no pain., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Karne et al.)

Objective: Transition of the United States Medical Licensing Examination Step 1 to a pass/fail structure has focused attention on medical student research in residency application. Previous studies have explored how various factors affect the neurosurgery match success, but none have focused on applicants from schools without a neurosurgery residency program., Methods: The authors compiled a list of neurosurgery residents matched from 2016 to 2022 from schools lacking a neurosurgery program. They gathered demographic and bibliometric data, focusing on academic productivity before residency. The distinction between the top 40 and non-top 40 programs used the 5-year institutional h-index (ih[5]-index) of departments., Results: Between 2016 and 2022, the gross number of students entering neurosurgery from schools without a home program rose from 15 to 26 in 2021, declining to 23 in 2022. The range of matched applicants per school was 0 to 10. The median number of publications per resident increased from 2 in 2016 to 5 in 2022 (p < 0.001). The lowest and highest numbers of publications by applicants were 0 and 40, respectively, with 22.5% reporting no publications. The lowest and highest h-indices by applicants were 0 and 11, respectively, with nearly one-third (31.2%) possessing an h-index of 0. Applicants from schools lacking a neurosurgery residency program who matched into top 40 programs had a publication range of 0-11, with a higher median of 3 compared with those who did not (median 2, range 0-8). While no significant differences were found in publication numbers (p = 0.084), a difference in h-index was observed (p = 0.024) between the two groups. Publications significantly correlated with the h-index, with each additional publication increasing the h-index by 0.19 (p < 0.001, adjusted R2 = 0.3348)., Conclusions: Median publication counts have increased in this cohort, but they do not distinguish top 40 program matches. Conversely, the h-index, correlating with publication quantity and journal impact factor, does.

Background: Macromastia, defined as the abnormal enlargement of breasts, burdens individuals physically and psychologically, impacting their daily lives beyond aesthetics. Reduction mammoplasty offers relief by restoring proportional breast volume and appropriate contour. Surgical success relies on choosing a suitable individualized operative technique tailored to the patient's presentation and postoperative goals. This study examines postoperative, patient-reported outcomes across different reduction techniques to gauge the impact of reduction technique on overall patient perspective of aesthetic and functional satisfaction., Methods: A retrospective review identified reduction mammoplasty patients by a single surgeon between 2018 and 2022. Exclusion criteria included augmentation-related or cancer reconstructive procedures. Phone interviews were conducted using a survey adapted from BREAST-Q to assess postoperative outcomes in patients. Data analysis included Pearson chi-square test in STATA 16.1., Results: Among 155 patients identified, 64 completed the survey. Average postsurgical interval was 24 months postoperative. After stratifying patients by operative technique, there was no significant difference in postoperative satisfaction among the cohorts with regard to nipple and breast appearance, sensation, symmetry, or shape., Conclusions: This study highlights no significant disparity in perceived aesthetic or functional outcomes among different reduction mammoplasty techniques. Personalized considerations, such as patient factors, surgical expertise, and anatomical specifics, should guide technique selection, emphasizing individualized approaches over presumed superior methods for optimal results., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The 1.6-megabase deletion at chromosome 3q29 (3q29Del) is the strongest identified genetic risk factor for schizophrenia, but the effects of this variant on neurodevelopment are not well understood. We interrogated the developing neural transcriptome in two experimental model systems with complementary advantages: isogenic human cortical organoids and isocortex from the 3q29Del mouse model. We profiled transcriptomes from isogenic cortical organoids that were aged for 2 and 12 months, as well as perinatal mouse isocortex, all at single-cell resolution. Systematic pathway analysis implicated dysregulation of mitochondrial function and energy metabolism. These molecular signatures were supported by analysis of oxidative phosphorylation protein complex expression in mouse brain and assays of mitochondrial function in engineered cell lines, which revealed a lack of metabolic flexibility and a contribution of the 3q29 gene PAK2. Together, these data indicate that metabolic disruption is associated with 3q29Del and is conserved across species.

Activation of zymogens within the pancreatic acinar cell is an early feature of acute pancreatitis. Supraphysiological concentrations of cholecystokinin (CCK) cause zymogen activation and pancreatitis. The effects of the CCK analog, caerulein, and alcohol on trypsin and chymotrypsin activation in isolated pancreatic acini were examined. Caerulein increased markers of zymogen activation in a time- and concentration-dependent manner. Notably, trypsin activity reached a peak value within 30 min, then diminished with time, whereas chymotrypsin activity increased with time. Ethanol (35 mM) sensitized the acinar cells to the effects of caerulein (10(-10) to 10(-7) M) on zymogen activation but had no effect alone. The effects of ethanol were concentration dependent. Alcohols with a chain length of >or=2 also sensitized the acinar cell to caerulein; the most potent was butanol. Branched alcohols (2-propanol and 2-butanol) were less potent than aliphatic alcohols (1-propanol and 1-butanol). The structure of an alcohol is related to its ability to sensitize acinar cells to the effects of caerulein on zymogen activation.

Acute pancreatitis is a disease that has many causes. Each cause seems to affect the acinar cell in some way that results in the premature activation and retention of potent proteolytic enzymes. These activated enzymes then injure the acinar cell and cause the immediate release of cytokines and activate the complement system. Together, these molecules attract and sequester inflammatory cells, in particular neutrophils, which causes further secretion of cytokines, free radicals, and other vasoactive molecules, such as nitric oxide. We propose that the released inflammatory molecules induce local effects, such as pancreatic edema and necrosis, and systemic complications, such as hypotension, tachycardia, fever, capillary leak syndrome, and hypoxia. The cytokines released in the pancreas also stimulate apoptosis, further enhancing the cell death response in pancreatitis. Much of the current research is aimed at understanding the links between these series of events and finding agents that can modulate the cascade of events involved in pancreatitis. What is promising in this endeavor is that the response produced with pancreatitis is nearly identical with all etiologies, suggesting that therapy may not have to be specific to a particular cause. The mechanistic models of AP presented herein are supported by preliminary clinical studies that suggest that protease and cytokine inhibitors may improve the course of AP in specific clinical settings.

A method for rapidly evaluating functional interactions between ligands and G-protein--coupled receptors has been developed. The technology is based on the ability of animals to change color by controlling the position of pigmented organelles within skin cells called melanophores. cDNA coding for a receptor to be studied is expressed in immortalized frog melanophores. Stimulation of a receptor that normally functions to activate either adenyl cyclase or phospholipase C induces centrifugal melanosome translocation and cell darkening. Conversely, application of an agonist to cells expressing a receptor that operates to inhibit adenyl cyclase induces centripetal pigment movement and cell lightening. The simple optical change can be used to investigate ligand-receptor interactions at several levels, including single-cell analysis and high-throughput chemical screening. Current efforts are focused on (1) identifying small peptides that activate or block thromboxane. A(2) and platelet-activating factor (PAF) receptors and (2) cloning eicosanoid receptors.

Vertebrate olfactory receptors are members of the seven-transmembrane-domain G protein-coupled receptor family. They utilize intracellular signal transduction pathways which are activated by stimulation of odorant receptors and use the second messengers cAMP and/or inositol 1,4,5-trisphosphate and diacylglycerol. Studies of how odorants bind to and activate the receptors can be considered part of the more general problem of how chemicals interact with G protein-coupled receptors. This review describes the development of a new technique for assessing functional interactions between chemicals and these receptors in only minutes. Predicted uses of the system include structure-function analyses of both G protein-coupled receptors and their ligands, studies of receptor coupling to G proteins and cloning of cDNAs for these receptors.