Postmenopausal Vaginal Microbiome and Microbiota

The ovulatory cycle has a significant influence on the microbial composition, according to the action of estrogen and progesterone on the stratified squamous epithelium, due to an increase in epithelial thickness, glycogen deposition, and influence on local immunology. The 16S rRNA gene amplification and pyrosequencing study demonstrated that healthy women have community state types (CST), classified as; type “L,” with a predominance of Lactobacillus crispatus, type II, with a predominance of Lactobacillus gasseri, type III, where Lactobacillus iners predominates, and type V with a predominance of Lactobacillus jensenii. Type IV does not identify lactobacilli but a heterogeneous population of bacteria. There seems to be a relationship between increased vaginal bacterial diversity and poverty of lactobacilli with the complaining of vaginal dryness. With menopause, there appears to be a reduction in lactobacilli associated with higher serum levels of follicle-stimulating hormone (FSH) and lower estrogen levels. The evaluation of Gram-stained vaginal smears in postmenopause women must take into account the clinical-laboratory correlation. We should observe two meanly possibilities, atrophy with few bacterial morphotypes, without inflammatory, infiltrate (atrophy without inflammation), and atrophy with evident inflammatory infiltrate (atrophy with inflammation or atrophic vaginitis). The relationship between the microbiome and postmenopausal vulvovaginal symptoms seems to be related to the bacterial vaginal population. However, more robust studies are needed to confirm this impression.

Immunophenotype of the inflammatory response in the central and enteric nervous systems of cockatiels (Nymphicus hollandicus) experimentally infected with parrot bornavirus 2

Proventricular dilatation disease is a lethal disease of psittacine birds. In this study, we characterized the local cellular immune response in the brain, proventriculus, and small intestine of 27 cockatiels ( Nymphicus hollandicus) experimentally infected with parrot bornavirus 2 (PaBV-2). Perivascular cuffs in the brain were composed of CD3+ T-lymphocytes and Iba1+ macrophages/microglia in most cockatiels (n = 26). In the ganglia of the proventriculus, CD3+ T-lymphocytes (n = 17) and Iba1+ macrophages (n = 13) prevailed. The ganglia of the small intestine had a more homogeneous distribution of these leukocytes, including PAX5+ B-lymphocytes (n = 9), CD3+ T-lymphocytes (n = 8), and Iba1+ macrophages (n = 8). Our results indicate that perivascular cuffs in the brain and the inflammatory infiltrate in the proventriculus of PaBV-2-infected cockatiels is predominately composed of T-lymphocytes, while the inflammatory infiltrates in the ganglia of the small intestine are characterized by a mixed infiltrate composed of T-lymphocytes, B-lymphocytes, and macrophages.

COVID-19

SARS-CoV-2 infection is characterized by its high contagiousness and unusual potential lethality. Microscopically, diffuse alveolar damage is the main histologic lung injury dominated by alveolar destruction. At the early stage, the authors note non-specific lesions similar to lesions of diffuse alveolar damage. In particular, the alveoli dilated and filled with exudative fibromyxoid material, the thickening of the interalveolar partitions by edema and an essentially mononuclear inflammatory infiltrate with eosinophilic hyaline membranes covering the alveoli. Viral inclusions are not generally found, and at an advanced stage, the installation of pulmonary fibrosis is noted. The place of non-invasive and/or invasive ventilation is undetermined in hypoxemic respiratory failure secondary to SARS-Cov-2 pneumonia, whereas in the most severe cases of COVID-19, the use of oxygenation by extracorporeal membrane is immediate. The cytokine storm in the lungs prompted clinicians to administer immunomodulators, the results of which was a reduction in hospital mortality.

RhoA, Claudin 18, and c-MET in Gastric Cancer: Clinicopathological Characteristics and Prognostic Significance in Curative Resected Patients

Background: Recently, markers related to molecular classification were suggested as promising therapeutic targets for treatment and prediction of prognosis in gastric cancer (GC), including c-MET, RhoA, and Claudin-18 (CLDN18). This study aimed to investigate their expression in GC and its correlation with clinicopathological characteristics and survival. Methods: We retrospectively evaluated GC patients who underwent curative gastrectomy. c-MET, RhoA, and CLDN18 were analyzed through immunohistochemistry (IHC), and groups for analysis were determined according to the median values obtained for each marker. Results: Among the 349 GC evaluated, 180 (51.6%), 59 (16.9%), and 61 (17.5%) patients were completely negative for c-MET, RhoA, and CLDN18, respectively. Total gastrectomy, D1 lymphadenectomy, poorly differentiated histology, and greater inflammatory infiltrate were more frequent in the c-MET-negative group. Diffuse type, greater inflammatory infiltrate, and advanced pT and pTNM stage were associated with low-RhoA GC. The venous invasion was more frequent in the low-CLDN18 group. Furthermore, c-MET was positively correlated with RhoA and negatively with CLDN18. HER2 expression was associated with c-MET-positive and high-CLDN18 GC; and loss of E-cadherin expression in c-MET-negative and low-RhoA GC. c-MET-negative and Low-RhoA were significantly associated with worse disease-free survival. Conclusions: c-MET, RhoA, and CLD18 expression occurred frequently in GC. RhoA GC had distinct clinicopathological characteristics related to prognosis. c-MET and RhoA were associated with survival but were not independent predictors of prognosis.

Does CD1a Expression Influence T Cell Function in Patients With Langerhans Cell Histiocytosis?

Langerhans cell histiocytosis lesions are characterized by CD1a+ myeloid lineage LCH cells and an inflammatory infiltrate of cytokines and immune cells, including T cells. T cells that recognize CD1a may be implicated in the pathology of many disease states including cancer and autoimmunity but have not been studied in the context of LCH despite the expression of CD1a by LCH cells. In this perspective article, we discuss the expression of CD1a by LCH cells, and we explore the potential for T cells that recognize CD1a to be involved in LCH pathogenesis.

Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease

Kidney tissues from cats with naturally occurring chronic kidney disease (CKD) and adult and senior cats without CKD were assessed to determine whether telomere shortening and nitrosative stress are associated with senescence in feline CKD. The histopathologic assessment of percent global glomerulosclerosis, inflammatory infiltrate, and fibrosis was performed. Senescence and nitrosative stress were evaluated utilizing p16 and iNOS immunohistochemistry, respectively. Renal telomere length was evaluated using telomere fluorescent in situ hybridization combined with immunohistochemistry. CKD cats were found to have significantly increased p16 staining in both the renal cortex and corticomedullary junction compared to adult and senior cats. Senior cats had significantly increased p16 staining in the corticomedullary junction compared to adult cats. p16 staining in both the renal cortex and corticomedullary junction were found to be significantly correlated with percent global glomerulosclerosis, cortical inflammatory infiltrate, and fibrosis scores. p16 staining also correlated with age in non-CKD cats. Average telomere length was significantly decreased in CKD cats compared to adult and senior cats. CKD cats had significantly increased iNOS staining compared to adult cats. Our results demonstrate increased renal senescence, telomere shortening, and nitrosative stress in feline CKD, identifying these patients as potential candidates for senolytic therapy with translational potential.

Suppurative meningoencephalitis secondary to a Trueperella pyogenes-induced mandibular abscess in a free-ranging gray brocket deer (Mazama gouazoubira)

Trueperella pyogenes is an opportunistic pathogen, most commonly affecting ruminants and pigs. A female free-ranging gray brocket deer (Mazama gouazoubira) had an abscess in the masseter muscle associated with an osteolysis and osteomyelitis in the adjacent right mandibule, with a fistulous tract to the orbit and through the optic foramen into the skull, causing a suppurative meningitis. Histologically, the abscess was characterized by a neutrophilic and histiocytic inflammatory infiltrate with myriad of Gram-positive rod-shaped bacteria, and a focally extensive suppurative and histiocytic leptomeningitis of the ventral portions of the brain. Aerobic microbiologic culture, MALDI-ToF, and PCR identified T. pyogenes.

Green and Chemical Silver Nanoparticles and Pomegranate Formulations to Heal Infected Wounds in Diabetic Rats

Infected cutaneous ulcers from diabetic rats with Candida albicans and Streptococcus aureus were treated with spray formulations containing green silver nanoparticles (GS), chemical silver nanoparticles (CS), or pomegranate peel extract (PS). After wound development and infection, the treatments were performed twice per day for 14 days. The wound healing was analyzed on days 2, 7, and 14 through the determination of CFUs, inflammatory infiltrate, angiogenesis, fibroplasia, myeloperoxidase, and collagen determination. Expressive improvement in wound healing was noted using both silver nanoparticles for 7 days. All the treatments were superior to controls and promoted significant S. aureus reduction after 14 days. CS presented better anti-inflammatory results, and GS and CS the highest number of fibroblasts. Despite the techniques’ limitations, GS and CS demonstrated considerable potential for managing infected wounds, especially considering no early strategies prior to the drugs, such as the debridement of these wounds, were included.

Association of Histopathological Parameters and Axillary Lymphnode Metastasis in Primary Breast Carcinoma

Introduction: The most common malignancy worldwide among females is breast carcinoma and the second most common malignancy in India, next to cervical cancer. A wide range of potential prognostic features have been studied in breast cancer and are mainly divided into two groups i.e. Histopathological and Molecular. The histological features are cost-effective and provide reliable diagnostic and prognostic information in these tumors. Axillary Lymph node status is one of the most important prognostic factors and greatly affects the morbidity and mortality of the patient. Materials and Methods: All breast cancer specimens received in the Department of Pathology over a period of five years. The following histopathological parameters were carefully studied like Tumor size, Histological type, Grade, Presence of necrosis, Inflammatory cell infiltrate, Lymphatic invasion, Blood vessel invasion, Perineural invasion, and other Stromal changes were studied in detail, and association of these histopathological parameters with axillary lymph node metastasis were analyzed. Results: A total of 100 cases were studied, and most of the patients were over the age of 50. The maximum number of cases was in the T2 stage (55%). Infiltrating ductal carcinoma (88%) was the most common type of tumor encountered in the study. The majority of the cases were Grade I tumors. Skin Invasion was seen in 14% and Lymphovascular Invasion was seen in 17% of cases respectively. There was a statistically significant association between the size of the tumor, T stage, Grade of the tumor, necrosis, and inflammatory infiltrate on further analysis. Conclusion: There was a statistically significant correlation between Tumor size, pathological T stage, Grade of the tumor, Necrosis and inflammatory infiltrate with axillary Lymph node metastasis in the present study. Increased tumor size, T stage, higher grade, presence of necrosis and low inflammatory infiltrate are associated with increased axillary Lymph node metastasis.

Impact of Epithelial–Mesenchymal Transition on the Immune Landscape in Breast Cancer

The impact of epithelial–mesenchymal transition (EMT) signature on the immune infiltrate present in the breast cancer tumor microenvironment (TME) is still poorly understood. Since there is mounting interest in the use of immunotherapy for the treatment of subsets of breast cancer patients, it is of major importance to understand the fundamental tumor characteristics which dictate the inter-tumor heterogeneity in immune landscapes. We aimed to assess the impact of EMT-related markers on the nature and magnitude of the inflammatory infiltrate present in breast cancer TME and their association with the clinicopathological parameters. Tissue microarrays were constructed from 144 formalin-fixed paraffin-embedded invasive breast cancer tumor samples. The protein expression patterns of Snail, Twist, ZEB1, N-cadherin, Vimentin, GRHL2, E-cadherin, and EpCAM were examined by immunohistochemistry (IHC). The inflammatory infiltrate in the TME was assessed semi-quantitatively on hematoxylin and eosin (H&E)-stained whole sections and was characterized using IHC. The inflammatory infiltrate was more intense in poorly differentiated carcinomas and triple-negative carcinomas in which the expression of E-cadherin and GRHL2 was reduced, while EpCAM was overexpressed. Most EMT-related markers correlated with plasma cell infiltration of the TME. Taken together, our findings reveal that the EMT signature might impact the immune response in the TME.