The retina consists of various cell types arranged in eight cell layers and two membranes that originate from the neuroectodermal cells. In this study, the timing of differentiation and distribution of the cellular components and the layers of the rabbit retina are investigated using light and electron microscopy and immunohistochemical techniques. There were 32 rabbit embryos and 12 rabbits used. The rabbit retina begins its prenatal development on the 10th day of gestation in the form of optic cup. The process of neuro- and gliogenesis occurs in several stages: In the first stage, the ganglionic cells are differentiated at the 15th day. The second stage includes the differentiation of Muller, amacrine, and cone cells on the 23rd day. The differentiation of bipolar, horizontal, and rod cells and formation of the inner segments of the photoreceptors consider the late stage that occurs by the 27th and 30th day of gestation. On the first week of age postnatally, the outer segments of the photoreceptors are developed. S100 protein is expressed by the Muller cells and its processes that traverse the retina from the outer to the inner limiting membranes. Calretinin is intensely labeled within the amacrine and displaced amacrine cells. Ganglionic cells exhibited moderate immunoreactivity for calretinin confined to their cytoplasm and dendrites. In conclusion, all stages of neuro- and gliogenesis of the rabbit retina occur during the embryonic period. Then, the retina continues its development postnatally by formation of the photoreceptor outer segments and all layers of the retina become established. RESEARCH HIGHLIGHTS: The aim of this study is to investigate the morphogenesis of the rabbit retina during pre- and postnatal life. The primordia of the retina could be observed in the form of the optic cup. The ganglionic cells are the first cells to differentiate, while the photoreceptor cells are the last. S100 protein is expressed by the Muller cells and its processes. Calretinin is intensely labeled in the amacrine and displaced amacrine cells and moderately expressed in the cytoplasm and dendrites of ganglionic cells.

This project aims to investigate the diagnostic performance of multiple overlapping-echo detachment imaging (MOLED) technique-derived transverse relaxation time (T2) maps in predicting progesterone receptor (PR) and S100 expression in meningiomas.
63 meningioma patients were enrolled from October 2021 to August 2022, who underwent a complete routine magnetic resonance imaging and T2 MOLED, which can characterize the whole brain transverse relaxation time within 32 seconds in a single scan. After the surgical resection of meningiomas, the expression levels of PR and S100 were determined by an experienced pathologist using immunohistochemistry techniques. Histogram analysis was performed in tumor parenchyma based on the parametric maps. Independent t test and Mann-Whitney U test were applied for the comparison of histogram parameters between different groups, with a significance level of P < .05. Logistic regression and receiver operating characteristic (ROC) analysis with 95% confidence interval were conducted for the diagnostic efficiency evaluation.
PR-positive group had significantly elevated T2 histogram parameters (P = .001-.049) compared to the PR-negative group. The multivariate logistic regression model with T2 showed the highest area under the ROC curve (AUC) for predicting PR expression (AUC=0.818). Additionally, the multivariate model also had the best diagnostic performance for predicting meningioma S100 expression (AUC=0.768).
The MOLED technique-derived T2 maps can distinguish PR and S100 status in meningiomas preoperatively.

Granular cell tumor (GCT) commonly presents in the subcutaneous tissue and head and neck region, and it is uncommon in the gastrointestinal tract. Experience with esophageal GCTs in the pediatric population is limited, with only 7 cases reported in the literature, 3 with eosinophilic esophagitis (EoE).
Case information from 11 pediatric patients with GCTs of the esophagus was retrieved. H&E and immunohistochemical slides were reviewed with clinical, endoscopic, and follow-up data from all patients.
In total, 7 male and 4 female patients were included, with ages ranging from 3 to 14 years. Indications for esophagogastroduodenoscopy (EGD) included EoE (n = 3), follow-up for Crohn disease, and other nonspecific complaints. Endoscopically, all patients had a single submucosal, firm mass protruding into the lumen, with normal overlying mucosa. The nodules were removed endoscopically in multiple fragments in all cases. Histologically, the tumors showed sheets and trabeculae of cells containing bland nuclei, inconspicuous nucleoli, and abundant pink granular cytoplasm without atypical features. All tumors were immunoreactive for S100, CD68, and SOX10. Follow-up showed that all patients were disease-free (median, 2 years).
We report the largest series of pediatric esophageal GCTs with coincidental association with EoE. These EGD findings are characteristic, and removal by biopsy is both diagnostic and therapeutic.

BACKGROUND: Encephaloceles are neural tube defects characterized by herniation of meninges, neural tissue and cerebrospinal fluid, while atretic cephaloceles denote a rudimentary connection to the intracranial space with absence of herniated neural tissue and represent an infrequent dermatopathologic diagnosis. Limited reports of these entities confound the challenge in their histopathologic distinction. Accurate classification is important given associated anomalies and neurologic manifestations that impact prognosis.
METHODS: We describe the clinicopathological and immunohistochemical [glial fibrillary acidic protein (GFAP), S100, epithelial membrane antigen (EMA), and somatostatin receptor subtype 2A (SSTR2A)] features in a retrospective series encountered at a single institution between 1994 and 2020.
RESULTS: We identified 13 cases classified as atretic cephalocele (n = 11) and encephalocele (n = 2). Hamartomatous changes and multinucleated cells were unique to atretic cephaloceles while myxoid areas were unique to encephaloceles. At least focal staining for SSTRA was seen in all atretic cephaloceles with the majority (87.5%) staining for EMA; negative staining for GFAP and S100 confirmed absence of neural tissue. Encephaloceles were GFAP and S100 positive, and negative for SSTR2 and EMA. Atretic cephaloceles had a favorable prognosis compared to encephaloceles, with severe morbidity present in both encephalocele cases.
CONCLUSIONS: Our study raises awareness of atretic cephalocele and encephalocele among dermatopathologists and reveals a mutually exclusive immunophenotype that facilitates their distinction for prognostication and management.

Ablative fractional resurfacing is clinically an efficient treatment for burn scar management. The aim of this pilot study was to investigate the poorly understood mechanisms underlying ablative fractional CO2 laser (AFL-CO2) therapy in relation to biomarkers S100 and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). S100 stains for Langerhans cells and neuronal cells, potentially representing the pruritus experienced. 11β-HSD1 catalyses the interconversion of cortisol and cortisone in cells, promoting tissue remodelling. Immunohistochemical analysis of S100 and 11β-HSD1 protein expression in the dermis and epidermis of the skin was performed on normal skin, before and after AFL-CO2 therapy. Data assessing outcome parameters was collected concurrently with the skin biopsies. 13 patients were treated with AFL-CO2 therapy. Langerhans cells decreased by 39% after 2nd treatment. Neuronal cells were overexpressed before treatment in the scar tissue by 91% but levels returned to that resembling normal skin. 11β-HSD1 expression in keratinocytes was significantly higher after laser treatment compared to before in scar tissue (p <0.01). No clear correlation was found in dermal fibroblast numbers throughout the treatment course. Whilst the role of the explored mechanisms and their association with clinical outcomes cannot conclusively be stated, this pilot study demonstrates promising trends that encourages investigation into this relationship.

Adenoid cystic carcinoma (ACC) is a distinctive tumour. Limited studies involving a large population have reported multicentre systematic analyses of the clinical, pathological and immunohistochemical (IHC) features of ACC as well as the potential role of IHC markers in the prognosis of ACC.
The clinical, histopathological and IHC data of 296 cases obtained from two tertiary hospitals were analysed. The age at onset ranged from 12 to 87 years with a median age of 52 years. The male-to-female ratio was 1:1.3. Patients with ACC arising from the lacrimal gland were younger than those with tumours arising from other sites. Patients with tumours in the extra auditory canal and nasopharynx were older than those with tumours in other locations. Histopathologically, solid type ACC was the most frequent in the nasal cavity and paranasal sinus (6/51) group. Tumours arising from the oral cavity most commonly showed perineural invasion (10/60) and margin positivity (11/60). IHC analyses showed that CK8/18, CK7, CK14, epithelial membrane antigen and CD117 were expressed in 35/35 (100%), 87/88 (98.8%), 26/27 (96.2%), 42/43 (97.6%) and 113/120 (94.1%) patients, respectively. CK5/6, P63, smooth muscle actin, calponin and S100 were positively expressed in 73/73 (100%), 111/124 (89.5%), 38/43 (88.3%), 41/50 (82.0%) and 61/92 (66.3%) cases, respectively. S100 proteins were expressed in 54 (54/77) primary cases and two (2/9) metastatic cases (p = 0.013).
ACC is a distinctive tumour that mainly affects middle-aged and elderly individuals, with a mild female predominance. Loss of expression of S100 proteins may be a poor prognostic factor associated with metastasis.

BACKGROUND: Crocus sativus L. has been used throughout the world in traditional medicine as a treatment for neurological disorders such as depression. Growing attention is currently being paid to the use of neuroprotective agents in ischemic strokes.
OBJECTIVE: This study assed the effect of saffron as a neuroprotective natural product in cerebral ischemia in human.
METHODS: Patients with acute ischemic stroke were randomly allocated to receive either routine stroke care (control group, n = 20) or routine care plus aqueous extract of saffron capsule (200 mg/day) (saffron-treated group, n = 19). Both groups were monitored during their four-day hospital stay and the three-month follow-up period. The groups were compared in terms of short- and long-term effects of saffron capsules using the National Institute of Health Stoke Scale (NIHSS), Barthel Scale, and serum neuron specific enolase (NSE), Brain-derived neurotrophic factor (BDNF), S100 levels.
RESULTS: Based on the NIHSS, the severity of stroke during the first four days was significantly lower in the saffron-treated group than in the control group (P < 0.05). Compared to the levels on the first day, serum NSE and s100 levels were significantly decreased and BDNF concentration was increased in the saffron-treated group on the fourth day. Also, our results showed there was a negative significant non-linear cubic regression between BDNF concentration and score of NIHSS. At the end of the three-month follow-up period, the mean Barthel index was significantly higher in the saffron-treated group than in the control group (P < 0.001).
CONCLUSIONS: The results of this study confirmed the short and long-term neuroprotective effects of aqueous extract of saffron on ischemic stroke in humans.

BACKGROUND: Following tissue injury after trauma, the activation of innate immune pathways results in systemic inflammation, organ failure and an increased risk of infections. The objective of this study was to characterize the kinetics of the S100A8/S100A9 complex, a new-recognized alarmin, as well as its soluble receptor sRAGE, over time after trauma as potential early biomarkers of the risk of organ damage.
METHODS: We collected comprehensive data from consenting patients admitted to an ICU following severe trauma. The blood samples were taken at Day 0 (admission), Day1, 3 and 5 S100A8/A9 and sRAGE were measured by ELISA. Biomarkers levels were reported as median (IQR).
RESULTS: Thirty-eight patients sustaining in majority a blunt trauma (89%) with a median ISS of 39 were included. In this cohort, the S100A8/A9 complex increased significantly over time (p = 0.001), but its levels increment over time (D0 to D5) was significantly smaller in patients developing infection (7.6 vs 40.1 mcg/mL, p = 0.011). The circulating level of sRAGE circulating levels decreased over time (p < 0.0001) and was higher in patients who remained in shock on day 3 (550 vs 918 pg/mL; p = 0.02) or 5 (498 vs 644 pg/mL; p = 0.045). Admission sRAGE levels were significantly higher in non-survivors (1694 vs 745 pg/mL; p = 0.015) and was higher in patients developing renal failure (1143 vs 696 pg/mL, p = 0.011).
CONCLUSIONS: Our findings reveal an interesting association between the biomarker S100A8/9 least increase over time and the presence of infectious complication after trauma. We describe that the sRAGE decline over time is in relation with shock and markers of ischemic injury. We also confirm the association of sRAGE levels measured at admission with mortality and the development of renal failure.
CONCLUSIONS: This work illustrates the importance of following the circulating level of biomarker overtime. The utilization of S1008/9 as a tool to stratify infection risk and trigger early interventions need to be validated prospectively.

BACKGROUND: This prospective study was undertaken to investigate the value of early S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) in prognosticating outcome in patients with poor-grade aneurysmal subarachnoid hemorrhage and to develop a statistical model and cutoff values for clinical practice.
METHODS: Between 2012 and 2014, patients with poor-grade subarachnoid hemorrhage (Hunt and Hess grade 3-5) who were admitted within 24 hours after hemorrhage were prospectively enrolled. Serum NSE and S100B levels were assayed once daily during the first 3 days after hemorrhage. Patient characteristics, Glasgow Coma Scale score, Hunt and Hess grade, and Fisher grade at admission were recorded. Glasgow Outcome Scale (GOS) score was obtained at 6 months and dichotomized as poor (score 1-3) or good (score 4-5). Logistic regression and receiver operating characteristic curve were used to assess the value of S100B and NSE in predicting outcome, and cutoff values were calculated using conditional interference trees.
RESULTS: The study included 52 patients. Hunt and Hess grade was 3 in 23 patients, 4 in 15 patients, and 5 in 14 patients. S100B range was 0.07-5.62 μg/L (mean 0.87 μg/L ± 1.06). NSE range was 5.7-94.2 μg/L (mean 16.1 μg/L ± 10.5). At 6-month follow-up, 23 patients (44.2%) had a poor outcome, and 29 patients (55.8%) had a good outcome. Both S100B at day 1 (P = 0.004; cutoff 0.202 μg/L) and NSE at day 1 (P = 0.047; cutoff 9.4 μg/L) predicted good outcome with a specificity of 100%. The specificity of mean S100B in detecting patients with poor outcome reached 100% (P = 0.003) when combined with mean NSE levels.
CONCLUSIONS: S100B and NSE measured during the first 3 days after hemorrhage showed, separately and combined, a significant predictive value in prognosticating clinical outcome in patients with poor-grade subarachnoid hemorrhage. A multicenter study with a large patient cohort is necessary to validate the above-mentioned cutoff values for clinical practice.

BACKGROUND: The outcome of the autograft therapy for Parkinson\'s disease including autologous cells from adrenal medulla was disappointing. This could be attributed to the pathological process in Parkinson\'s disease affecting cells of the adrenal medulla. This study was performed to investigate the histopathological changes in the adrenal medulla of AS/AGU rat, a model of Parkinson\'s disease, in comparison with Albino Swiss (AS) rats.
METHODS: A total of 24 male AS rats were divided into four groups, each of 6 animals: AS W1 - AS rats aged 1 week; AS adult - AS adult rats; AS/ /AGU W1 - AS/AGU rats aged 1 week; and AS/AGU adult - AS/AGU adult rats. The rats were sacrificed and the adrenal glands were dissected and processed for histological staining with haematoxylin and eosin and periodic acid Schiff and for immunohistochemical staining for S100 protein, ubiquitin and tyrosine hydroxylase.
RESULTS: The histological investigation of the adrenal medulla of AS/AGU rats showed vascular congestion, inflammatory cellular infiltration, pyknotic nuclei, necrotic chromaffin cells and medullary inclusion bodies. The immunohistochemical investigation of AS/AGU rats showed a statistically significant decrease in the expression of S100 protein, ubiquitin and tyrosine hydroxylase compared to AS rats.
CONCLUSIONS: The histological and immunohistological changes in the adrenal medulla could explain the failure of outcome of adrenal autograft therapy in Parkinson\'s disease.