Endoscopic, Histologic, and Composite Endpoints in Patients with Ulcerative Colitis Treated with Etrasimod [106/120 characters, including spaces].

BACKGROUND & AIMS: Histologic remission, a potentially important treatment target in ulcerative colitis (UC), is associated with favorable long-term outcomes. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. This post-hoc analysis of the ELEVATE UC program evaluated the efficacy of etrasimod according to histologic and composite (histologic/endoscopic/symptomatic) endpoints and examined their prognostic value. METHODS: Patients with moderately to severely active UC were randomized 2:1 to once-daily oral etrasimod 2 mg or placebo. Histologic and composite endpoints, including disease clearance (endoscopic/histologic/symptomatic remission), were assessed at Weeks 12 (ELEVATE UC 52; ELEVATE UC 12) and 52 (ELEVATE UC 52). Logistic regressions examined associations between baseline and Week 12 histologic/composite endpoints and Week 52 outcomes. RESULTS: At Weeks 12 and 52, significant improvements with etrasimod vs placebo were observed in histologic/composite outcomes, including endoscopic improvement-histologic remission (EIHR) and disease clearance. The proportion of patients treated with etrasimod achieving clinical remission (CR) at Week 52 was higher among those with disease clearance at Week 12 vs those without disease clearance (73.9% [17/23] vs 28.3% [71/251]). Histologic improvement and endoscopic improvement (EI) at Week 12 were moderately and strongly associated with CR at Week 52, odds ratio (OR) (95% confidence interval [CI]): 2.37 (1.27, 4.41) and 6.36 (3.47, 11.64), respectively. Histologic remission and EI at Week 12 were strongly associated with EIHR at Week 52, OR (95% CI): 3.21 (1.70, 6.06) and 5.47 (2.89, 10.36), respectively. CONCLUSIONS: Etrasimod was superior to placebo for achievement of stringent histologic and composite endpoints; NCT03945188, NCT03996369.

The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.

PURPOSE: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. METHODS: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. RESULTS: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). CONCLUSION: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

Tumor necrosis in magnetic resonance imaging predicts urothelial carcinoma with squamous differentiation in muscle-invasive bladder carcinoma.

PURPOSE: This study investigated radiologic features on preoperative MRI to differentiate urothelial carcinoma with squamous differentiation (UCSD) from conventional urothelial carcinoma (UC) in muscle-invasive bladder carcinoma. METHODS: Ninety-nine patients who underwent radical cystectomy and a preoperative bladder MRI scan within three months before surgery were retrospectively enrolled. Various MRI features, including tumor length, location, multiplicity, long-to-short axis ratio, morphology, radiologic stage, and degree of severe necrosis, were analyzed. Univariable and multivariable logistic regression analyses were performed to identify MRI features predictive of UCSD. The diagnostic performance of a significant MRI feature was assessed using 5-fold cross-validation. RESULTS: Among the MRI features, significant radiologic findings associated with UCSD in the univariable analysis included heterogeneous tumor signal intensity in T2-weighted images (odds ratio [OR], 3.365; 95% confidence interval [CI], 1.213-9.986; P = 0.022) and contrast-enhanced T1-weighted images (OR, 4.428; 95% CI, 1.519-12.730; P = 0.007), as well as marked (≥ 50%) severe necrosis (OR, 17.100; 95% CI, 4.699-73.563; P < 0.001). In the multivariable analysis, marked (≥ 50%) severe necrosis (odds ratio [OR], 13.755; 95% confidence interval [CI], 2.796-89.118; P = 0.004) was a significant predictor of UCSD. Marked (≥ 50%) severe necrosis showed a high specificity of 95.0% with a precision of 65.0% for diagnosing UCSD based on 5-fold cross-validation. CONCLUSION: Preoperative bladder MRI revealing marked severe necrosis may be indicative of UCSD and can assist in distinguishing it from conventional UC.

The regulatory effects of water probiotic supplementation on the blood physiology, reproductive performance, and its related genes in Red Tilapia (Oreochromis niloticus X O. mossambicus).

Probiotics are becoming increasingly popular as eco-friendly alternatives in aquaculture. However, there is limited research on their impacts on the reproductive efficiency of Red Tilapia (Oreochromis niloticus x O. mossambicus) broodstock. Therefore, this experiment aimed to explore the combined effects of selective probiotics Bacillus subtilis and B. licheniformis (BSL; 1:1) added to water on blood hematology, serum metabolites, gonadal histology, reproductive performance, and reproductive associated genes in Red Tilapia broodstock. Tilapia broodfish weighing 140-160 g were stocked in four treatment groups: control (T0), and the other three groups were added different levels of BSL to the water as follows: T1 (0.01 g/m3), T2 (0.02 g/m3), and T3 (0.03 g/m3), respectively. Results indicate that BSL administration significantly improved RBCs, hemoglobin, hematocrit, MCH, and MCHC, with the highest improvement seen in the T3 group (P < 0.05). BSL added to the fish water significantly enhanced serum protein fractions (total protein, albumin, and globulins), while AST, ALT, ALP, creatinine, uric acid, and glucose were significantly diminished in a dose-dependent way (P < 0.05). Adding 0.02-0.03 g/ m3 of BSL resulted in higher antioxidant status (superoxide dismutase and catalase) compared to other groups (P < 0.05). Testosterone levels were higher in T3 than in other groups (P < 0.05). All female hormones (LH, FSH, estradiol, and progesterone) were substantially augmented by the addition of BSL. Additionally, the BSL groups exhibited higher GSI, HSI, VSI (male only), egg diameter (mm), mean number of fry/fish, and mean fry weight (g) compared to the control group (P < 0.05). Expression of reproductive-associated genes (vasa, nanos1a, nanos2, dnd1, pum1, AMH, and vtg) were significantly up-regulated in the gonads of fish in the 0.03 g/m3 treatment. The histological gonadal structure exhibited that BSL improved gonad maturation in both genders of Tilapia fish. Overall, adding a mixture of B. subtilis and B. licheniformis (0.03 g/m3 water) can accelerate reproductive performance in Red Tilapia through up-regulation of reproductive genes and enhance the health profile.

A Solitary Peutz-Jeghers Hamartomatous Polyp in the Gastric Body: A Case Report.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant genetic condition characterized by the development of hamartoma-type intestinal polyposis and areas of skin pigmentation, among other signs. Additionally, the occurrence of solitary Peutz-Jeghers polyps is exceedingly rare. We present the case of a 50-year-old female with a medical history of hypothyroidism, chronic gastritis, and dyslipidemia, who presented with dyspeptic symptoms and occasional rectal bleeding. Endoscopic examination revealed a solitary hamartomatous polyp in the gastric body and other gastrointestinal abnormalities. The patient underwent treatment and is being monitored with regular endoscopic studies and evaluations for other potential neoplasms. This case underscores the importance of considering the syndrome as a potential differential diagnosis. It emphasizes the necessity of a multidisciplinary approach to managing and monitoring such cases, particularly the early detection of possible neoplasms.

Dysphagia and chest pain in a 7-year-old girl.

Dysphagia is a common gastrointestinal complaint in the pediatric population and should raise concern for oropharyngeal as well as esophageal disorders. We describe a 7-year old patient who was admitted to the hospital for sudden onset dysphagia, abdominal pain, and decreased oral intake. Extensive evaluations including endoscopy eventually revealed herpes simplex esophagitis as well as eosinophilic esophagitis. Herpes simplex esophagitis is a rare condition in the immunocompetent population and is typically self-resolving. Eosinophilic esophagitis is a chronic, inflammatory condition characterized by esophageal eosinophilia and signs of esophageal dysfunction. The concurrent presentation of both conditions in the pediatric population has rarely been described.

Decellularization of Rat Submandibular Gland for Salivary Gland Tissue-Engineering Applications.

OBJECTIVES: This study describes a robust and versatile method for decellularization of rat submandibular glands (SMGs). METHODS: Briefly, rat SMGs were harvested and subjected to perfusion cycles using an anionic detergent. Native and decellularized SMG tissues were subjected to histological analysis using hematoxylin and eosin (H&E) stain and immunohistochemical staining using Hoescht reagent. Further, complementary DNA was synthesized using the native and decellularized SMG tissues and subjected to quantitative reverse transcription polymerase chain reaction (RT-PCR) using rat-specific genes (i.e., α-amylase [Amyl], aquaporin 5 [Aqp5], mucin 19 [Muc19] and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]). The total DNA within native and decellularized SMG tissues were also quantified. RESULTS: H&E staining of SMG tissues revealed preserved ECM content. Decellularized SMG scaffolds lacked cellular material but retained collagen bundles similar to native SMGs. Hoechst reagent immunostaining showed cell nuclei and DNA present in native SMG but not in decellularized SMG scaffolds. Quantitative RT-PCR analysis showed specific amplification products of salivary gland-specific genes (Amyl, Muc19 and Aqp5) and GAPDH in the native SMG tissues. However, no amplification product was observed in the cDNAs from the decellularized SMG scaffolds, confirming the absence of DNA. Quantification of the DNA content showed that the decellularized SMG scaffolds had significantly lower DNA content than native SMG tissue. CONCLUSIONS: Results from this study demonstrated that the decellularization protocol was effective in removing cellular material while preserving the extracellular matrix components and structural integrity of the native SMG tissue.

The intricate relationship between obesity, type 2 diabetes and female breast cancer: A retrospective study of 335 women.

Background: Type 2 diabetes (T2D) is a risk factor for female breast cancer (FBC). Obesity has also been associated with FBC, also depending on menopausal status. This study aimed to evaluate the impact of obesity and T2D on the development, aggressiveness, and invasiveness of FBC. Methods: Demographic, clinical, and histopathological data from 335 women with FBC were collected, and analyzed according to weight category (102 normal weight, 117 overweight, and 116 living with obesity) and the presence/absence of T2D. Results: Age at oncologic diagnosis was not statistically significantly different for body weight; women with overweight or obesity were more likely to have an oncologic diagnosis after menopause than normal weight (p < 0.001). The presence of overweight/obesity and T2D seemed to be associated with a higher incidence of metastasis, recurrence, and triple-negative breast cancer (TNBC) subtype (p < 0.001). Excess body weight was also associated with high histologic grade (G3) (p < 0.005). Conclusions: These results confirm excess body weight and T2D as unfavorable prognostic factors in terms of the presence of the TNBC subtype, tumor metastasis, recurrence, and aggressiveness (G3 and Ki-67 > 20%). This study highlights the importance of prevention in all women, with early screening, and adequate nutritional programs.

Histological characterization of HIFU lesions.

Background: High intensity focused ultrasound (HIFU) can destroy tissue by thermal ablation which may be accompanied by acoustic cavitation and/or tissue water boiling, but the biological and histological effects of these treatments have not been fully documented. Here, detailed histological analysis over time using well characterized HIFU exposures in in vivo rat livers is described.Methods: Exposures used invoked either (i) thermal, with acoustic cavitation and/or tissue water boiling or (ii) predominantly thermal damage. Cavitation activity was detected using both active and passive methods. Histological assessment involved hematoxylin and eosin (H&E), picrosirius red and immunohistochemical staining.Results: Distinct concentric damage regions were identified after HIFU exposures. The outermost ring showed a red H&E-stained rim that was characterized by hemorrhage. The adjacent inner band appeared white due to increased extracellular spaces. The morphology of the next zone depended on the exposure. Where there was no tissue acoustic cavitation/water boiling, this was the lesion center, in which heat-fixed cells were seen. Where acoustic cavitation/boiling occurred, a centermost zone with irregular holes up to several hundred microns across was seen. Cleaved caspase-3 and Hsp70 staining in the periphery of both types of HIFU exposures was seen within the outermost ring of hemorrhage, where an inflammatory response was also observed. By day 7, a distinct acellular region in the center of the HIFU lesions had been created.Conclusions: These results identify the morphological effects and elucidate the similarities and differences of HIFU-induced thermal lesions in the presence or absence of acoustic cavitation/tissue water boiling.

Gaze cueing improves pattern recognition of histology learners.

Experts perceive and evaluate domain-specific visual information with high accuracy. In doing so, they exhibit eye movements referred to as "expert gaze" to rapidly focus on task-relevant areas. Using eye tracking, it is possible to record these implicit gaze patterns and present them to histology novice learners during training. This article presents a comprehensive evaluation of such expert gaze cueing on pattern recognition of medical students in histology. For this purpose, 53 students were randomized into two groups over eight histology sessions. The control group was presented with an instructional histology video featuring voice commentary. The gaze cueing group was presented the same video, but with an additional overlay of a live recording of the expert's eye movements. Afterward, students' pattern recognition was assessed through 20 image-based tasks (5 retention, 15 transfer) and their cognitive load with the Paas scale. Results showed that gaze cueing significantly outperformed the control group (p = 0.007; d = 0.40). This effect was evident for both, retention (p = 0.003) and transfer tasks (p = 0.046), and generalized across different histological contexts. The cognitive load was similar in both groups. In conclusion, gaze cueing helps histology novice learners to develop their pattern recognition skills, offering a promising method for histology education. Histology educators could benefit from this instructional strategy to provide new forms of attentional guidance to learners in visually complex learning environments.

Decalcification-free technique on the analysis of dental pulp tissue: histological and immunohistochemical analysis.

BACKGROUND: Histological techniques are essential for the microscopic study and investigation of the human dental pulp. The aim of this study was to evaluate the impact of decalcification-free technique by examining dental pulp morphology by histological staining with haematoxylin and eosin and immunohistochemistry. MATERIALS AND METHODS: The sample consisted of 30 healthy third molars extracted for orthodontic indication, the pulp tissue was obtained by removing the mineralized tissues, separating the enamel and dentine and by marking with a flexible diamond disc on the coronal surface and longitudinal axis of the root. These guides made it possible to separate the fragments and obtain the pulp tissue for fixation and staining with H&E and subsequent immunohistochemistry with CD34 and S-100 antibodies. RESULTS: The technique showed preservation of pulp morphology with adequate preservation of microscopic structures. No alterations in tissue viability were observed. The staining allowed an accurate assessment of vascular and nervous components by means of CD34 and S-100 markers, respectively. CONCLUSIONS: This technique allows preservation of pulp tissue, maintaining viable tissue for histological analysis and immunohistochemistry tests, as well as reducing sample processing time.

Prevalence and classification of meniscal calcifications in the human knee.

OBJECTIVE: To investigate the occurrence of meniscal calcifications in individuals with and without knee osteoarthritis (OA). Additionally, we aim to identify the specific types of calcifications: basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP). METHOD: We analyzed 82 meniscal posterior horn samples (medial and lateral) collected from 41 human subjects. Among them, 20 individuals underwent total knee replacement due to medial compartment OA, while 21 deceased donors had no known knee OA. The assessment of meniscal calcifications and Pauli's histopathological scoring was conducted using histological sections. Furthermore, adjacent sections underwent measurement using Raman spectroscopy to characterize BCP and CPP calcifications based on their distinct spectral fingerprints. RESULTS: All OA individuals exhibited calcifications in at least one meniscus, compared to 9.5% (95%CI 1%, 30%) of donors. Among 35 OA menisci with calcifications, 28(80%) had BCP, 5(14%) had CPP and 2(6%) had both types. In 4 donor menisci, 3(75%) had CPP while 1(25%) had both types. We estimated the association between Pauli score and presence of BCP in OA individuals, yielding an odds ratio of 2.1 (95%CI 0.8, 5.3) per 1 Pauli score. The association between Pauli score and presence of CPP (in whole study sample) seemed weaker, with odds ratio of 1.3 (95%CI 1.1, 1.7). CONCLUSION: The presence of BCP was predominant in menisci of OA individuals, whereas CPP exhibited similar prevalence in individuals with and without OA. The formation of BCP crystals in menisci may represent an important and specific characteristic of OA disease process that warrants further attention.

Multiple-biomarker approach in the assessment of bisphenol A effect on the grooved carpet clam Ruditapes decussatus (Linnaeus, 1758).

BACKGROUND: Bisphenol A (BPA), a plastic additive monomer, is among the most highly produced chemicals worldwide, and is broadly used in many industries, such as food and beverage containers, milk bottles, and paper products. Previous studies demonstrated that BPA has potential toxicity to aquatic organisms, causing endocrine disturbance and behavioural disorders. The current work aimed to determine the toxic impacts of BPA on the edible marine clam Ruditapes decussatus considering a multi-biomarker approach (mortality, biochemical studies, DNA strand breaks using comet assay, and histopathological examinations with semi-quantitative and quantitative histopathological analyses). The clams were exposed under laboratory conditions to three concentrations of BPA (0 "control", 1, and 5 µg/L) for a period of 21 days. After the exposure period, BPA impacts were assessed in the digestive gland as a versatile and environmentally relevant organ for ecotoxicological studies. RESULTS: In BPA-treated clams, mortality (10%) occurred only at the highest BPA concentration (5 µg/L). Biochemical impairments were detected in a concentration-dependent manner as a consequence of BPA exposure. There were significant increases in malondialdehyde (MDA) and glutathione (GSH) levels, while catalase (CAT) activity was significantly reduced. Our results revealed that BPA induced neurotoxicity in R. decussatus, as evidenced by the inhibition of acetylcholinesterase (AChE) activity in a dose-dependent manner. Furthermore, DNA damage was strongly induced as BPA levels increased. Additionally, our results have been affirmed by alterations in digestive gland tissues at BPA treatments, which consequently can impair the clam's ability for food absorption; these alterations included mainly atrophic and necrotic digestive tubules, epithelial cell vacuolization, hemocyte infiltration, and intertubular fibrosis. Based on the data obtained from the semi-quantitative and quantitative histopathological analyses, the exposure of the clam's digestive gland to BPA with concentrations of 1 and 5 µg/L for 21 days showed significant histopathological alterations compared with the control clams. CONCLUSION: The multi-biomarker approach used in the current study proved to be a useful tool for assessing the impact of diphenylmethane compounds, such as BPA. Water-borne BPA causes oxidative stress, neurotoxicity, genotoxicity, and deleterious effects on the clam digestive gland; all of these could deteriorate clam performance and health, causing tissue dysfunction.

Malignant Hypercalcemia Revealing Pulmonary Sarcoidosis.

Sarcoidosis is a systemic disorder characterized by the development of granulomatous inflammation in various organs of the body. Hypercalcemia is one of its manifestations. We present a case of malignant hypercalcemia in a 77-year-old man, diagnosed as sarcoidosis following multiple assessments and histological confirmation showing noncaseating granulomas. In the absence of an etiological diagnosis, treatment was initially based on hydration, diuretics, and bisphosphonate. Glucocorticoid therapy can be the standard treatment for hypercalcemia related to sarcoidosis.

An anatomical study of the subarachnoid space surrounding the trigeminal ganglion in horses-in preparation for a controlled glycerol rhizotomy in equids.

Introduction: Equine trigeminal-mediated headshaking is a painful neuropathic disorder comparable to trigeminal neuralgia in humans. The selective destruction of pain fibers within the trigeminal ganglion, called rhizotomy, is the surgical treatment of choice for idiopathic trigeminal neuralgia refractory to medical treatment in humans. The human trigeminal ganglion is enclosed by a dural recess called the Meckel's or trigeminal cave, in which the ganglion is surrounded by a cerebrospinal fluid (CSF)-filled subarachnoid space. During glycerol rhizotomy, glycerol is percutaneously injected in this CSF-filled space. Until now, information about the anatomy of the dural recess and the subarachnoid space surrounding the trigeminal ganglion is lacking in horses. The aim of this study was to explore if a CSF-filled subarachnoid space around the trigeminal ganglion exists in horses. Materials and methods: Six equine cadaver heads were investigated for CSF accumulation around the ganglion with a 3 Tesla MRI. After anatomical dissection to expose the trigeminal root, a polymer-based radiopaque contrast agent was injected through the porus trigeminus into the subarachnoid space (cisternography). The exact delineation and the volume of the contrast agent accumulation were determined on subsequent micro-computed tomographic scans and segmentation. Finally, the distribution of the contrast agent within the subarachnoid space was examined histologically in three specimens. Results: In all 12 specimens included in this study, the trigeminal ganglion was surrounded by a subarachnoid space forming a trigeminal cistern. The mean volume of the trigeminal cave in this study was 0.31 mL (±SD: 0.11 mL). Distribution of the contrast agent along the peripheral nerves (i.e., ophthalmic, maxillary and/or mandibular nerve) was observed in 7 out of 12 specimens. Discussion/conclusion: A subarachnoid space surrounding the trigeminal ganglion exists in the horse and could be targeted for glycerol rhizotomy in horses suffering from trigeminal-mediated headshaking. However, the clinical relevance of contrast agent distribution along the peripheral nerves remains to be assessed.

Conjoint transcriptomics and metabolomics analyses provide insights into the toxicity of acetamiprid to Lethenteron reissneri larvae.

The neonicotinoid pesticide acetamiprid has been widely used in agricultural pest control and was frequently detected in the water environment. There have been some studies of the toxic effects of acetamiprid on fish, but studies on aquatic lower vertebrates are still very limited. As a primitive jawless vertebrate, Lethenteron reissneri has a special position in evolution and is now listed as a national second level protected animal in China. The present study aimed to investigate the toxic effect of acetamiprid on the liver of L. reissneri larvae. A conjoint analysis of the transcriptomics and metabolomics was performed to determine the responses of L. reissneri larvae liver to acetamiprid at different concentrations (L for low concentration 25 mg/L and H for high concentration 100 mg/L). Even low concentrations of acetamiprid can cause significant liver damage to L. reissneri larvae in a short period. In omics analyses, 2141 differentially expressed genes (DEGs) and 183 differentially abundant metabolites (DAMs) were identified in the H/Control group, and 229 DEGs and 144 DAMs were identified in the L/C group. Correlation analyses revealed acetamiprid affected the metabolic pathways of L. reissneri larvae liver such as the glycerophospholipid metabolism and arachidonic acid metabolism. This study not only enriches the basis for understanding the toxic effect of acetamiprid exposure to L. reissneri larvae liver and provides more information on the breeding and conservation of L. reissneri, but also further causes attention on toxicity risk from acetamiprid to aquatic lower vertebrate species.

Correlative three-dimensional X-ray histology (3D-XRH) as a tool for quantifying mammalian placental structure.

Mammalian placentas exhibit unparalleled structural diversity, despite sharing a common ancestor and principal functions. The bulk of structural studies in placental research has used two-dimensional (2D) histology sectioning, allowing significant advances in our understanding of mammalian placental structure. However, 2D histology sectioning may be limited if it does not provide accurate information of three-dimensional (3D) tissue architecture. Here, we propose correlative 3D X-ray histology (3D-XRH) as a tool with great potential for resolving mammalian placental structures. 3D-XRH involves scanning a formaldehyde-fixed, paraffin embedded (FFPE) tissue block with 3D X-ray microscopy (microCT) prior to histological sectioning to generate a 3D image volume of the embedded tissue piece. The subsequent 2D histology sections can then be correlated back into the microCT image volume to couple histology staining (or immunolabelling) with 3D tissue architecture. 3D-XRH is non-destructive and requires no additional sample preparation than standard FFPE histology sectioning, however the image volume provides 3D morphometric data and can be used to guide microtomy. As such, 3D-XRH introduces additional information to standard histological workflows with minimal effort or disruption. Using primary examples from porcine, bovine, equine, and canine placental samples, we demonstrate the application of 3D-XRH to quantifying placental structure as well as discussing the limitations and future directions of the methodology. The wealth of information derived from 2D histological sectioning in the biomedical, veterinary, and comparative reproductive sciences provides a rich foundation from which 3D-XRH can build on to advance the study of placental structure and function.

FInCH: FIJI plugin for automated and scalable whole-image analysis of protein expression and cell morphology.

Study of morphogenesis and its regulation requires analytical tools that enable simultaneous assessment of processes operating at cellular level, such as synthesis of transcription factors (TF), with their effects at the tissue scale. Most current studies conduct histological, cellular and immunochemical (IHC) analyses in separate steps, introducing inevitable biases in finding and alignment of areas of interest at vastly distinct scales of organization, as well as image distortion associated with image repositioning or file modifications. These problems are particularly severe for longitudinal analyses of growing structures that change size and shape. Here we introduce a python-based application for automated and complete whole-slide measurement of expression of multiple TFs and associated cellular morphology. The plugin collects data at customizable scale from the cell-level to the entire structure, records each data point with positional information, accounts for ontogenetic transformation of structures and variation in slide positioning with scalable grid, and includes a customizable file manager that outputs collected data in association with full details of image classification (e.g., ontogenetic stage, population, IHC assay). We demonstrate the utility and accuracy of this application by automated measurement of morphology and associated expression of eight TFs for more than six million cells recorded with full positional information in beak tissues across 12 developmental stages and 25 study populations of a wild passerine bird. Our script is freely available as an open-source Fiji plugin and can be applied to IHC slides from any imaging platforms and transcriptional factors.

A Retrospective Comparison of Diagnostic Tools of Bullous Pemphigoid for Elderly Patients.

BACKGROUND: Older patients who are predisposed to bullous pemphigoid (BP) may exhibit reluctance to undergo skin biopsy due to potential complications. OBJECTIVES: This study aimed to conduct a comparative evaluation among histology, direct immunofluorescence (DIF), and indirect immunofluorescence (IIF) to determine the optimal diagnostic tool in elderly patients. METHODS: A retrospective study was conducted on 841 patients suspected of having BP. All cases were initially classified as BP and non-BP in accordance with the diagnostic criteria. Student's t-test and chi-squared test examined differences between the 2 groups. We evaluated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio detected by the 3 tools. We stratified the analysis by age to compare the performance of the diagnostic tools and examined the risk factors associated with BP using logistic regression. RESULTS: Overall, histology exhibited the highest sensitivity (89.4%), while DIF demonstrated the highest specificity (67.1%). In the elderly, the IIF test exhibited the highest specificity (57.5%), the highest positive likelihood ratio (2.047), and the lowest negative likelihood ratio (0.226). Among patients taking Dipeptidyl Peptidase-4 (DPP-4) inhibitors, IIF demonstrated the highest positive likelihood ratio (3.194) and the second-lowest negative likelihood ratio (0.235). CONCLUSIONS: In cases that elderly patients suspected of having BP are reluctant to undergo skin biopsy, IIF demonstrates the optimal diagnostic method due to its highest positive likelihood ratio, the lowest negative likelihood ratio among the 3 diagnostic measures. Moreover, IIF is found to be a more effective tool for detecting BP in patients using DPP-4 inhibitors.

The Impact of Low-Power Therapeutic Lasers at 904†nm on the Healing Process of Wounds and the Relationships Between Extracellular Matrix Components and Myofibroblasts.

The goal of the study was to further our understanding of the functions that myofibroblasts do, how they interact with the matrix's extracellular elements, and how laser therapy at 904 nm works. Thirty Wistar rats with superficial wounds on the backs were used in this study. The laser therapy device used two energy levels of a 904 nm laser with an output power of 60 mW. The outcomes had been evaluated for one, three, five, seven, and fourteen days following laser therapy. Numerous methods, including as histology, immunohistochemistry, and scanning electron microscopy, have been used to evaluate the tissues.There was a statistically important (P ≤ .05) decrease in the number of inflammatory cells and the degree of edema after laser therapy. On the other hand, the amounts of elastic fiber as well as collagen slightly increased. On the third post-laser treatment day, there was a statistically significant distinction (P < .05) in the number of myofibroblasts with the desmin; smooth muscle alpha-actin phenotype between the laser-treated and control groups.These results suggest that, compared to a higher energy of 5.6 J, laser therapy at a lower energy of 3.6 J may be more effective in stimulating myofibroblast differentiation during the initial phases of wound healing. These findings show how low-power laser therapy promotes wound healing.