Mild Lesions Research Articles

Assessment of Toxicity and Biological Effects of α-Pinene on Morphine Tolerance and Dependence in Mice

Background: Research shows that α-Pinene interacts with the opioidergic system. Objectives: This study aims to examine the toxicity and the effects of α-Pinene on morphine tolerance and dependence in mice. Methods: Guidelines No. 423 and No. 407 were used to investigate acute and sub-chronic toxicity, respectively. For sub-chronic toxicity analysis, the animals were sacrificed on day 28, and blood and tissue samples were collected. After inducing morphine tolerance or dependence, in both phases, animals received i.p. vehicle, diazepam (5 mg/kg), and α-Pinene (3.125, 6.25, and 12.5 mg/kg). Withdrawal signs were recorded for 30 minutes. Results: Only the acute dose of α-Pinene showed mortality in animals, but mild lesions were seen in the brain, liver, and kidneys in the mice receiving its subchronic dose. Moreover, ALT, AST, ALP, and TG levels increased (P < 0.05) in female mice. Besides, 6.25 and 12.5 mg/kg (P < 0.001) of α-Pinene and only its high dose (12.5 mg/kg) (P < 0.001) reduced the number of jumps in the tolerance and dependence phases, respectively. Diarrhea (P < 0.001), writhing (P < 0.001), rearing, and climbing (P < 0.05 and P < 0.001, respectively) behaviors decreased in the tolerance phase, and grooming, climbing, and teeth chattering declined in the dependence phase (P < 0.001). Conclusions: The LD50 of α-Pinene was lower than 2000 mg/kg, but its subchronic dose caused mild tissue toxicities and biochemical changes. Moreover, α-Pinene decreased morphine tolerance and dependence and possibly was useful for the treatment of opioid dependence after complimentary trials.

Antimalarial Effects of Ethanolic Leaf Extracts of Azadirachta indica and Ocimum gratissimum, and Their Histologic Effects on Some Organs (Liver, Kidney and Heart) of Plasmodium berghei Infected Albino Mice

Azadirachta indica (Neem) and Ociumum gratissimum (clove Basil) have long been employed locally for the management of malaria. The present study compared antimalaria activities of the ethanolic leaf extracts of the individual plants, and assessed their combined effects on some organs of malaria-infected mice, at the Parasitology and Histopathology units, Federal Medical Centre (FMC), Owerri, from January to March, 2021. The leaves of the different plants were extracted with absolute ethanol (BDL 95%) for the test. Clean albino mice were experimentally infected intraperitoneally with chloroquine-sensitive Plasmodium berghei NK65 strain. Parasitaemia level was determined before parasite inoculation and at 24 hours post treatment period. Histopathological study on the liver, kidney, and heart was carried out using the Paraffin Setions method. Extracts of the leaves were administered orally, while chloroquine administration was intramuscular. The efficacy of the leaf extracts was tested on the P. berghei infected albino mice using the 4-day curative test. The lethal median dose (LD50) recorded for neem and clove basil leaf extracts were 31.62 and 1246.9 mg/kg body weight, respectively. Significant activity against the parasite was produced by infected mice treated with extracts of A. indica and O. gratissimum, and their combinations throughout the treatment period (P<.05). Highest reduction of parasitaemia was observed on day 4. Maximum parasitaemia reduction (78.65%) was attained with 30mg/kg of the combined extracts on the 7th day. Mild pathological lesions were observed in mice treated with A. indica leaf extract. These observations indicate better anti-malaria activity of the combination therapy as compared with the individual extracts of A. indica and O. grassimum, and indicate good antimalarial and protective roles of the plant extracts on the parasitized mice at large, as it slows down development of resistance.

The synergy of serum SFRP5 levels and the TyG index in predicting coronary artery disease and prognosing major adverse cardiovascular events.

Secreted frizzled-related protein 5 (SFRP5) is a member of the SFRP family that is known for its potent anti-inflammatory properties. Nevertheless, little is known regarding the relevance of SFRP5 in coronary artery disease (CAD). The current study examined the correlation between serum levels of SFRP5 and the triglyceride-glucose (TyG) index in patients who underwent coronary angiography (CAG) as a component of cardiovascular assessment and for the purpose of prognosis evaluation. A total of 310 hospitalized patients were enrolled in this study between May 2021 and March 2022 and were divided into three groups based on their CAG results and SYNTAX (synergy between PCI with TAXUS drug-eluting stent and cardiac surgery) scores: the control group, mild lesion group, and moderate-severe lesion group. Univariate and multivariate analyses were employed to investigate the relationships between changes in patients and clinical variables. To investigate the impact of the TyG index and serum SFRP5 levels on the occurrence of major adverse cardiovascular events (MACEs), Kaplan‒Meier curves were plotted. Serum SFRP5 levels were measured utilizing an enzyme-linked immunosorbent assay (ELISA) kit. The serum SFRP5 levels significantly decreased with the increasing severity and complexity of CAD, while the TyG index significantly increased (P < 0.001). Moreover, a significant negative correlation was observed between the serum SFRP5 levels and the TyG index (r = -0.312, P < 0.001). SFRP5 exerts a protective role in different groups of patients. The area under the receiver operating characteristic (ROC) curve indicated that an SFRP5 concentration > 115.58 pg/mL was the best predictive value for CAD (OR:0.87, P < 0.001). MACEs were significantly associated with serum SFRP5 levels and the TyG index, as indicated by both univariate and multivariate Cox regression analyses (P < 0.001). Furthermore, Kaplan‒Meier analysis indicated that as the TyG index decreased and SFRP5 levels increased, the occurrence of MACEs decreased (P < 0.001). Patients with a concentration of SFRP5 > 115.58 pg/mL and a TyG index < 8.49 exhibited a better prognosis for avoiding MACEs (P < 0.001). These results suggest that the collaboration between serum SFRP5 levels and the TyG index holds promise in predicting CAD and its prognosis.

Transplacental infection by bovine alphaherpesvirus type 1 induces protein expression of COX-2, iNOS and inflammatory cytokines in fetal lungs and placentas

Bovine alphaherpesvirus type 1 (BoAHV-1) is associated with respiratory and reproductive syndromes. Until present the immunologic mechanisms involved in BoAHV-1 abortion are partially known. We studied key elements of the innate immune response in the placentas and fetal lungs from cattle experimentally-inoculated with BoAHV-1. These tissues were analyzed by histopathology. Furthermore, virus identification was performed by qPCR and the expression of the inflammatory cytokines such as tumor necrosis factor-alpha, interleukin 1-alpha and inflammatory mediators like inducible nitric oxide synthase and cyclooxeganse-2 was evaluated by immunohistochemistry. The viral transplacental infection was confirmed by the detection of BoAHV-1 by qPCR in the placenta and fetal organs, which revealed mild inflammatory lesions. Inducible nitric oxide synthase immunolabelling was high in the lungs of infected fetuses and placentas, as well as for tumor necrosis factor-alpha in the pulmonary parenchyma and cyclooxeganse-2 in fetal annexes. However, the expression of interleukin 1-alpha was weak in these organs. To our knowledge, this is the first study that provides strong evidence of an early immune response to BoAHV-1 infection in the conceptus. Advances in the knowledge of the complex immunological interactions at the feto-maternal unit during BoAHV-1 infection are needed to clarify the pathogenesis of abortion.

Therapeutic Nucleic Acids against Herpes Simplex Viruses

The Herpes simplex virus (HSV) causes a wide range of diseases, ranging from relatively mild primary skin lesions to severe and often fatal episodes of encephalitis. Currently, the most effective drugs for HSV-infected people are nucleoside analogs (e.g., acyclovir) targeting enzymes encoded by viral DNA. The effectiveness of nucleoside analogs is reduced because of poor solubility in water, rapid intracellular catabolism, high cellular toxicity, and the appearance of resistant viral strains. Antisense technology that exploits nucleic acid fragments (NA-based agents) is a promising alternative to antiviral therapy due to the high affinity of these agents to target nucleic acids, their high solubility in water, and lower cellular toxicity. In the last decade, antisense oligonucleotides have been investigated as potential drugs for various diseases associated with “harmful” nucleic acids. Oligonucleotides with different chemical modifications targeted at specific regions of the HSV genome have shown effectiveness in suppressing the virus. siRNA-based agents have demonstrated prolonged and effective (up to 99%) inhibition of HSV replication. Based on the publications reviewed in the review over the past 30 years, it can be concluded about the prospects of using NA-based agents to combat herpes viral infections.

Can MRI predict olfactory loss and improvement in posttraumatic olfactory dysfunction?

Although most patients with post-traumatic olfactory dysfunction (PTOD) undergo MRI, there is no consensus about its diagnostic or prognostic value. The aims were: 1) to classify the extent of post-traumatic neurodegeneration; 2) to determine its relationship with chemosensory dysfunction (smell, taste, trigeminal); and 3) to establish whether MRI can predict olfactory improvement. We conducted a retrospective cohort study based on a series of 56 patients with PTOD. All patients underwent validated psychophysical tests of their smell, taste, and trigeminal functions, otorhinolaryngologic evaluation, and MRI. An experienced radiologist blinded to patient data evaluated 40 chemosensory-relevant brain regions according to a four-point scale (0=no lesion to 3=large lesion). Follow up data after 4 years (on average) were available in 46 patients. The cluster analysis showed 4 brain lesion patterns that differed in lesion localization and severity. They are associated with diagnostic categories: anosmia, hyposmia and normosmia. Two clusters were highly specific for anosmia (100% specificity)and could accurately predict this condition (100% positive predictive value). No clusters were associated with trigeminal or taste dysfunction. Regarding improvement, 72.7% of patients in the cluster with mild lesions experienced subjective and measurable olfactory improvement whereas this was only the case in 21.7-37.5% of patients with larger lesions. The odds of subjective smell improvement were 5.9 times higher in patients within the milder cluster compared to larger ones. The analysis of brain lesions in PTOD allows corroboration of smell test results and prediction of subjective and measurable improvement.

Polioencephalomalacia in Buffaloes in the Amazon Biome.

The epidemiological and clinical pathological aspects of polioencephalomalacia (PEM) in five buffaloes in the Amazon biome are described. Epidemiological data were obtained during the clinical visit in which buffalos were submitted to an examination of the nervous system. The diagnosis of PEM was based on epidemiological, clinical-pathological, and histopathological findings, similar to findings in other ruminants. In the clinical examination, all buffaloes had a body score between 2.5 and 3 (scale from 1 to 5), with decreased alertness, postural changes, marked hypermetria when stimulated to move, total or partial blindness demonstrated by colliding with the corral structures, head pressing and circumduction of the hindquarters when supported on the thoracic limbs, opisthotonos, muscle tremors, convulsions, paddling movements, sialorrhea, decrease in palpebral and pupillary reflexes, and eyeball rotation placing the pupillary slit in a vertical position. At necropsy, mild lesions characterized by edema and flattening of the cerebral convolutions were observed. A histopathological examination showed laminar necrosis of the cerebral cortex. The cause of PEM in the studied buffaloes was not established, which indicates the need for further studies to elucidate this disease in the species, particularly in the Amazon region.

Study of Cellular and Humoral Immunity and Histopathology of Target Tissues Following Newcastle Clone12IR Vaccine Administration in SPF Chickens.

Newcastle disease (ND) is a highly contagious viral infection affecting poultry production in many countries. Strict biosecurity and the administration of live attenuated vaccines against the ND virus (NDV) are the main implements of controlling programs. This study evaluated the efficacy and potency of the Razi Clone12IR Newcastle vaccine in specific pathogen-free (SPF) chickens. Chickens were vaccinated with either the Razi Clone12IR vaccine (group A1, n=20) or an imported Clone vaccine (B1, n=20) in the first week of life and boosted in the second week via eye drop, while negative control chickens received PBS (C1, n=20). Half of the birds in each group were challenged with the virulent NDV strain in the third post-vaccination week (A2, B2, and C2 groups). Specific antibody responses were determined in the collected sera by the hemagglutination inhibition (HI) assay for up to eight weeks. Cell-mediated immunity (CMI) was determined by the lymphocyte proliferation assay three and six weeks after the second vaccination. Sections of the tissues and organs, including the trachea, lungs, cecal tonsils, spleen, the bursa of Fabricius, liver, and small intestine, were subjected to histopathology. The immunized groups A1 and B1 showed significantly higher HI antibody titers before the challenge than the control group. In addition, lymphocyte proliferation responses significantly increased in the peripheral blood of the vaccinated groups. After the challenge, the A2 and B2 groups conferred good protection and drastically reduced virus shedding. No main lesions were noted in the tissues or organs of the vaccinated group in histopathology. In a few cases, mild microscopic lesions were observed, including the infiltration of inflammatory cells, which was related to the effect of the vaccine virus. These results indicate that the Razi Clone12IR vaccine is safe and can be an efficient tool for NDV infections by inducing protective humoral and CMI responses.

The Importance of 1-Year Protocol Biopsy in the Long-Term Prognosis of Kidney Transplants—5-Years Follow-Up

Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in every transplant center. There is no established regimen for performing them. The study aimed to evaluate if protocol biopsies can improve long-term patient outcomes after detecting early disorders and modifying treatment. Our observational study included 61 patients who underwent protocol biopsy 12 months after the transplantation. Based on the biopsy results, patients with abnormal histologic material (n=37) were divided into 3 study groups as follows: patients with mild inflammatory lesions (n=21), patients with interstitial fibrosis and tubular atrophy (IFTA) grade II to III (n=12), and patients with BK virus nephropathy (n=4). The control group (n=24) included kidney recipients with IFTA 0 to I grade. Outcomes after 5-year follow-up were evaluated. Five years after the biopsy, patients in the control group had stable graft function (5-year change in serum creatinine was -0.09 mg/dL). An increase in serum creatinine levels was observed in patients with IFTA II to III compared with the control group (0.14 mg/dL, P=.04). Immunosuppressive treatment was modified in the group with mild inflammatory changes and in the BKV group after the biopsy result. In the group with mild inflammatory lesions, renal function was stable (change of serum creatinine was -0.01 mg/dL, P=.51). In the BKV nephropathy group, there was a significant reduction in serum creatine levels (-0.48 mg/dL, P=.016). The analysis showed no diagnostic value for serum creatinine concentration (95% CI 0.49-0.78, P=.08). Protocol biopsies are useful for detecting early pathologies and preventing allograft failure. They greatly benefit patients with detectable pathology that can be treated or in whom therapy modification is possible.

Mpox-related ophthalmic disease. A rare case report.

Monkeypox virus (Mpox), a double-stranded DNA virus belonging to the Orthopox genus, can affect vulnerable anatomic sites, including the eyes, causing a monkeypox-related ophthalmic disease. The Mpox virus may enter the eye via autoinoculation and cause multiple problems from mild lesions including conjunctivitis, blepharitis, keratitis, to severe ones such as corneal ulcers, corneal scarring, and rarely loss of vision. The aim of this article is to aggregate from an ophthalmologic point of view what is presently known about Mpox related ophthalmic disease (MpoxROD) and to present a particular case of a 41-year-old, white, bisexual, HIV positive male, with severe ocular complications. This article presents the first reported case in Romania, of severe MpoxROD, with clinically relevant information for infectious disease doctors and especially for ophthalmologists.

DIAGNOSIS OF ENCEPHALITOZOON CUNICULI IN NEW ZEALAND RABITS BY SOME HISTOLOGICAL METHODS

The aim of this study was to determine the histopathological lesions associated with Encephalitozoon cuniculi (E. cuniculi) infection in 25 New Zealand rabbits randomly selected in a laboratory animal center. Microscopic lesions were evaluated on sample slides stained with HE, Gram, and Immunohistochemistry (IHC) techniques. Mild and moderate lesions included granulomatous inflammation, meningitis, and perivascular cuffing were identified in brain samples; interstitial nephritis and renal fibrosis were identified in the kidneys of 21 out of 25 rabbits. Among the 21 rabbits, the percentage of spore identification by HE and Gram staining methods were 9.5% and 71%, respectively while IHC revealed parasite antibody in 81% of the rabbits. Thus, laboratory New Zealand rabbits in Vietnam might be infected with high prevalence of E. cuniculi. Postmortem diagnosis with HE technique can be used for screening [i]while Gram and IHC staining can confirm the infections. The rabbit husbandry units should consider appropriate methods for infection assessment and control.&#x0D; &#x0D; [i]

Impact of Diabetic Lesions on Pathology, Treatment and Outcomes of Glomerular Diseases.

We aimed to evaluate whether concomitant diabetic glomerulosclerosis (DGS) and its severity impact the treatment and outcomes of primary glomerular diseases (GD) with comorbid diabetes. We conducted a retrospective review of people with diabetes and GD. We searched the Glomerular Disease Collaborative Network for biopsies from 2008 to 2015 among persons with diabetes and any of the following diagnoses: Focal Segmental Glomerulosclerosis (FSGS), IgA Nephropathy (IgAN), Minimal Change Disease (MCD), Membranous Nephropathy (MN) or Anti-Neutrophil Cytoplasmic Autoantibody Glomerulonephritis (ANCA GN). Data were abstracted from health records and histologic diabetic glomerular class scored. The primary composite endpoint was end-stage kidney disease (ESKD) or death. Multivariable Cox regression models tested whether any or the severity of diabetes histopathology impacted the primary endpoint. Data from 134 cases were available for analysis (78 DGS+GD and 56 GD alone). Diabetes duration and glycemic control were similar between the two groups (p=0.2; p=0.09, respectively). Use of immunosuppression did not differ between the two groups (p=0.3). The composite endpoint was significantly higher in DGS+GD [22.5 cases per 100 p-y (95% CI: 16.6-30.5)] versus GD alone [10.2 cases per 100 p-y (95% CI: 6.4-16.2)]. Regression analyses demonstrated that compared to the GD alone group, the risk for the composite endpoint was similar in the group with mild DGS+GD (DGS class 1, 2a) [HR=1.15 (95% C: 0.54-2.43)], while the group with severe DGS+GD (DGS class 2b, 3, 4) had a greater risk [HR=3.60 (1.79-7.22)]. Among people with diabetes and GD, mild diabetic glomerular lesions on biopsy do not impact outcomes, but moderate-severe lesions increase the risk for ESKD and death. Whether use of immunosuppression, particularly glucocorticoids, is less successful in inducing GD remission in people with moderate-severe diabetic lesions will be a focus of future study in a larger population.

Porcine Respiratory Coronavirus (PRCV): Isolation and Characterization of a Variant PRCV from USA Pigs.

Porcine respiratory coronavirus (PRCV), a mutant of the transmissible gastroenteritis virus (TGEV), was first reported in Belgium in 1984. PRCV typically replicates and induces mild lesions in the respiratory tract, distinct from the enteric tropism of TGEV. In the past 30 years, PRCV has rarely been studied, and most cited information is on traditional isolates obtained during the 1980s and 1990s. Little is known about the genetic makeup and pathogenicity of recent PRCV isolates. The objective of this study was to obtain a contemporary PRCV isolate from US pigs for genetic characterization. In total, 1245 lung homogenate samples from pigs in various US states were tested via real-time PCR targeting PRCV and TGEV RNA. Overall, PRCV RNA was detected in five samples, and a single isolate (ISU20-92330) was successfully cultured and sequenced for its full-length genome. The isolate clustered with a new group of variant TGEVs and differed in various genomic regions compared to traditional PRCV isolates. Pathogens, such as PRCV, commonly circulate in pig herds without causing major disease. There may be value in tracking genomic changes and regularly updating the diagnostic methods for such viruses to be better prepared for the emergence of variants in ecology and pathogenicity.

Cefditoren pivoxil induced toxic epidermal necrolysis: a case report

Cutaneous adverse drug reactions vary in severity, from mild erythematous skin lesions to life-threatening toxic epidermal necrolysis. Antiepileptics, antipsychotics, antimicrobials, and diuretics are associated with these adverse reactions. We report a case of cefditoren pivoxil-induced toxic epidermal necrolysis in a 46-year-old Indian woman who presented initially with a maculopapular rash that eventually progressed to steroid-refractory toxic epidermal necrolysis. The patient succumbed to her illness on day 33 of the index rash following septic shock.

Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta-analysis.

The question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta-analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions. PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random-effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses. Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81-0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17-1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69-0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30-2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15-1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37-2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47-1.70), Hp eradication had no advantage compared to placebo or no treatment. Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.

Comparison between two scoring methods to assess tail damage of docked pig carcasses during postmortem inspection in Ireland.

Tail inspection in the abattoir is a tool to help determine the welfare status of pigs. However, methodologies vary widely. Moreover, meat inspection is moving from palpation and incision towards visual-only (VIS) examination. This study investigated whether a VIS examination was sufficient to detect tail damage compared to handling (HAND), which ensures examination of all aspects of the tail. The severity of tail skin damage (0 [undamaged] - 4 [partial/full loss of tail]) and presence/absence of bruises was scored using both methods after scalding/dehairing of 5498 pig carcasses. There was a good relationship between methods when evaluating tail skin damage (sensitivity, 82.48%; specificity, 99.98%; accuracy, 98.98%; correlation ρ = 0.84). The results were similar for the presence of bruises (sensitivity, 74.98%; specificity, 99.09%; accuracy, 89.94%; correlation ρ = 0.79). However, the percentage of tails classified as undamaged was higher using VIS (69.9%) than HAND (63.55%) examination. Conversely, VIS detected fewer mild lesions (score 1 - 13.64%; score 2 - 11.73%) than HAND (score 1 - 15.21%; score 2 - 15.53%). A higher percentage of bruises was detected using HAND than VIS (37.96% vs. 29.03%). Visual evaluation is a valid alternative to handling evaluation of carcass tail damage and bruising.

A Weakly Supervised Deep Learning Framework for Whole Slide Classification to Facilitate Digital Pathology in Animal Study.

The pathology of animal studies is crucial for toxicity evaluations and regulatory assessments, but the manual examination of slides by pathologists remains time-consuming and requires extensive training. One inherent challenge in this process is the interobserver variability, which can compromise the consistency and accuracy of a study. Artificial intelligence (AI) has demonstrated its ability to automate similar examinations in clinical applications with enhanced efficiency, consistency, and accuracy. However, training AI models typically relies on costly pixel-level annotation of injured regions and is often not available for animal pathology. To address this, we developed the PathologAI system, a "weakly" supervised approach for WSI classification in rat images without explicit lesion annotation at the pixel level. Using rat liver imaging data from the Open TG-GATEs system, PathologAI was applied to predict necrosis of n = 816 WSIs (377 controls). TG-GATEs studied 170 compounds at three dose levels (low, middle, and high) for four time points (3, 7, 14, and 28 days). PathologAI first preprocessed WSIs at the tile level to generate a high-level representation with a Generative Adversarial Network architecture. The prediction of liver necrosis relied on an ensemble model of 5 CNN classifiers trained on 335 WSIs. The ensemble model achieved notable classification accuracy on the holdout test set: 87% among 87 control slides free of findings, 83% among 120 controls with spontaneous necrosis, 67% among 147 treated animals with spontaneous minimal or slight necrosis, and 59% among 127 treated animals with minimal or slight necrosis caused by the treatment. Importantly, PathologAI was able to discriminate WSIs with spontaneous necrosis from those with treatment related necrosis and discriminated mild lesion level findings (slight vs minimal) and between treatment dose levels. PathologAI could provide an inexpensive and rapid screening tool to assist the digital pathology analysis in preclinical applications and general toxicological studies.

Unveiling a Shared Precursor Condition for Acne Keloidalis Nuchae and Primary Cicatricial Alopecias.

Small observational studies suggest subclinical disease occurrence in the normal-appearing scalp zones of several primary cicatricial alopecias. To aid patient management, we began routinely evaluating the entire scalp of patients with acne keloidalis nuchae (AKN), including trichoscopy-guided biopsies. This retrospective study evaluated 41 patients sequentially presenting with AKN at a single clinic between June and December 2022. Primary lesions and normal-appearing scalp in the superior parietal scalp at least 5 cm away from AKN-affected zones were clinically evaluated, and areas showing perifollicular erythema or scales/casts on trichoscopy were biopsied and histologically analyzed. Forty-one men with AKN, including 20 men of African descent, 17 Hispanic, and 4 European-descended Whites, were evaluated. All patients, including 22% with associated folliculitis decalvans, showed scalp-wide trichoscopy signs of perifollicular erythema or scaling in normal-appearing scalp areas. All patients showed histologic evidence of perifollicular infundibulo-isthmic lymphocytoplasmic infiltrates and fibrosis (PIILIF), with 96% showing Vellus or miniaturized hair absence. PIILIF was often clinically mistaken for seborrheic dermatitis (44-51%). All White patients had mild papular acne keloidalis nuchae lesions mistaken for seborrheic dermatitis. PIILIF may be a precursor to a wide spectrum of primary cicatricial alopecias, including AKN and folliculitis decalvans. This finding carries implications for the early diagnosis and management of AKN and other primary cicatricial alopecias.

Task Cortical Connectivity Reveals Different Network Reorganizations between Mild Stroke Patients with Cortical and Subcortical Lesions.

Accumulating efforts have been made to investigate cognitive impairment in stroke patients, but little has been focused on mild stroke. Research on the impact of mild stroke and different lesion locations on cognitive impairment is still limited. To investigate the underlying mechanisms of cognitive dysfunction in mild stroke at different lesion locations, electroencephalograms (EEGs) were recorded in three groups (40 patients with cortical stroke (CS), 40 patients with subcortical stroke (SS), and 40 healthy controls (HC)) during a visual oddball task. Power envelope connectivity (PEC) was constructed based on EEG source signals, followed by graph theory analysis to quantitatively assess functional brain network properties. A classification framework was further applied to explore the feasibility of PEC in the identification of mild stroke. The results showed worse behavioral performance in the patient groups, and PECs with significant differences among three groups showed complex distribution patterns in frequency bands and the cortex. In the delta band, the global efficiency was significantly higher in HC than in CS (p = 0.011), while local efficiency was significantly increased in SS than in CS (p = 0.038). In the beta band, the small-worldness was significantly increased in HC compared to CS (p = 0.004). Moreover, the satisfactory classification results (76.25% in HC vs. CS, and 80.00% in HC vs. SS) validate the potential of PECs as a biomarker in the detection of mild stroke. Our findings offer some new quantitative insights into the complex mechanisms of cognitive impairment in mild stroke at different lesion locations, which may facilitate post-stroke cognitive rehabilitation.

Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.

Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis. In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions. Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.