Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects.

Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High-Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine, and D-serine, as well as their precursors L-glutamine, L-asparagine, and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle, and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty.

Effectiveness of phototherapy with and without probiotics for the treatment of indirect hyperbilirubinaemia in preterm neonates: a randomised controlled trial.

INTRODUCTION: Raised serum bilirubin levels can cause kernicterus, and premature infants are at increased risk owing to metabolic immaturity. The standard treatment for neonatal jaundice is phototherapy, but probiotics alone can reduce the duration of phototherapy and hospitalisation. OBJECTIVES: To determine the effectiveness of phototherapy with and without probiotics for the treatment of indirect hyperbilirubinaemia in preterm neonates. PATIENTS AND METHODS: The open-labelled randomised controlled trial was conducted from January 2022 to January 2023 in the neonatal unit of the University of Lahore Teaching Hospital, Pakistan. A total of 76 preterm neonates who fulfilled the selection criteria were included and divided into two groups. Both groups received standard phototherapy. In Group B, a probiotic (Saccharomyces boulardii) 125 mg, twice daily, orally (in 5 cc of whichever milk the infant was receiving) was given until discharge from hospital. The primary outcome measurements were the duration of phototherapy and the length of hospitalisation. RESULTS: The mean (SD) duration of phototherapy was 36.55 (14.25) hours in Group A and 24.61 (9.25) hours in Group B (p <0.05). The mean (SD) duration of hospital stay was 47.36 (16.51) hours in Group A and 33.13 (8.93) hours in Group B (p <0.05). CONCLUSION: Oral probiotics (Saccharomyces boulardii) have a significant effect on the duration of phototherapy for neonatal hyperbilirubinaemia, and they decrease the chances of nosocomial infection. Exploration of clinical outcomes by investigating faecal flora and undertaking large randomised controlled trials of various probiotics are needed. ABBREVIATIONS: ABE: acute bilirubin encephalopathy; CNS: central nervous system; GA: gestational age; IVIG: intravenous immunoglobulin; KSD: kernicterus; NNU: neonatal unit; RCT: randomised controlled trial; S. boulardii: Saccharomyces boulardii.

Effect of Nasal Continuous Airway Pressure With and Without Surfactant Administration for the Treatment of Respiratory Distress Syndrome in Preterm Neonates.

Background Neonatal respiratory distress syndrome is a common cause of respiratory distress in newborns, often resulting from a lack of surfactant production or premature lung breakdown. The objective of this study was to compare the effect of nasal continuous airway pressure with and without surfactant administration for the treatment of respiratory distress syndrome in preterm neonates. Methodology A comparative analytical study was conducted on 100 neonates (group A continuous positive airway pressure (CPAP) with surfactant = 50 vs. group B CPAP only= 50 ). The group was allocated to the patient according to sequence. In group A, the neonates were given surfactant by the INSURE (intubation, surfactant, extubation) technique via an endotracheal tube with a single dose of 100 mg/kg/dose within the first hours of life followed by CPAP. In group B, the neonates were given only CPAP after birth. At follow-up after 24 hours, pH, pCO2, pO2, positive end-expiratory pressure (PEEP), and FiO2 were documented. All information was recorded on a predesigned questionnaire and results were subjected to statistical analysis to determine the significance of observed differences. Collected data were entered and analyzed using SPSS version 22 (IBM Corp., Armonk, NY, USA). Both groups were compared for mean pH, pCO2, pO2, PEEP, and FiO2 using an independent-sample t-test and effectiveness using a chi-square test. A significant difference was considered when the p-value was ≤0.05. Results Group A had a mean age of 4.84 ± 0.95 hours, while group B had a mean age of 5.5 ± 1.26 hours (p = 0.04). Gender distribution was similar in both groups, with 46.0% males and 54.0% females in group A, and 48.0% males and 52.0% females in group B (p = 0.841). Regarding post-treatment blood gas analysis, group A had a mean pH of 7.30 ± 0.05, and group B had a mean pH of 7.302 ± 0.07. While there was no significant difference in pO2 levels (p = 0.38), there was a substantial difference in pCO2 levels, with group A at 38.26 ± 4.35 and group B at 35.45 ± 4.36 (p = 0.02).CPAP parameters also showed a statistically significant difference in PEEP pCO2, with group A at 4.5 ± 0.73 and group B at 4.16 ± 0.37 (p = 0.004). After treatment, group A exhibited significant improvements in blood gas analysis and CPAP parameters compared to group B. Conclusions The study revealed that both CPAP with and without surfactant treatment effectively treat respiratory distress syndrome in preterm infants, with both being safe, effective, secure, and reducing side effects. However, CPAP treatment without surfactant is a non-invasive and cost-effective option.

The effect of chemotherapies on the crosstalk interaction between CD8 cytotoxic T-cells and MHC-I peptides in the microenvironment of WHO grade 4 astrocytoma.

INTRODUCTION: CD8 + T-cells and MHC-I have been detected in brain gliomas with a significant outcome. The effect of chemotherapies on the crosstalk interaction between CD8 + T-cells and MHC-I has never been explored. MATERIAL AND METHODS: The protein expression profiling of CD8 cytotoxic T-cells and the gene expression assay of MHC-I in 35 patients diagnosed with WHO grade 4 astrocytoma were performed. The impact of these two factors on tumor recurrence was analyzed. RESULTS: IDH was wildtype in 13 tumors. MHC-I protein expression was absent or low in 34 tumors and dense in a single case. MHC-I gene expression was upregulated in 10 tumors and 25 tumors showed MHC-I gene downregulation. Temozolomide (TMZ) was given to 24 patients and 11 patients received TMZ plus other chemotherapies. No statistically significant association was observed between IDH mutation and CD8 + T-cells ( p = 0.383). However, this association was significant in recurrence-free interval (RFI) ( p = 0.012). IDH-wildtype tumors with highly infiltrated CD8 + T-cells or IDH-mutant tumors with low CD8 + T-cells showed late tumor recurrence. There was a statistically significant difference in RFI between tumors with different MHC-I expression and CD8 + T-cell counts after treatment with TMZ or TMZ plus ( p = 0.026). CONCLUSIONS: No association between IDH mutation and CD8+ cytotoxic T-cell was found. IDH is directly linked to tumor recurrence regardless of CD8 + T-cells infiltration. TMZ plus other adjuvants is proved to be more effective in improving patient survival and delaying tumor recurrence, as compared to using TMZ alone. Nonetheless, none-TMZ adjuvants may increase tumor sensitization to cytotoxic T-cells more than TMZ.

A Comparison of Nifedipine Versus a Combination of Nifedipine and Sildenafil Citrate in the Management of Preterm Labour.

Background Preterm delivery is a significant contributor to neonatal and infant morbidity and mortality. Preventive methods are preferable to treatment protocols for reducing perinatal mortality and morbidity. The calcium channel blocker nifedipine has the potential to be employed as a tocolytic, whereas the phosphodiesterase inhibitor sildenafil citrate promotes smooth muscle relaxation. Objective This study aims to examine the tocolytic effect of nifedipine in combination with sildenafil citrate in managing preterm labour (PTL). Methods After approval from the ethical board, 160 patients fulfilling the selection criteria were enrolled in the study from the outpatient and emergency department of obstetrics and gynaecology, University of Lahore, Pakistan. After taking written informed consent, their demographic profile, i.e., name, age, gestational age at presentation, parity, and expected date of delivery was noted. Patients were randomly assigned in a 1:1 ratio to two study groups (Group A: sildenafil citrate + nifedipine) and (Group B: nifedipine) using a computer-generated random number table to obtain a trial sequence. In group A, each patient was given nifedipine 20 mg orally, followed by 10 mg orally every eight hours for 48 hours and vaginal administration of sildenafil citrate, 25 mg at eight-hour intervals, for 48 hours. In group B, females were given nifedipine 20 mg orally, followed by 10 mg orally every 8 hours for 48 hours. They were kept admitted for 72 hours. SPSS Statistics version 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) was used to enter and analyse the collected data. Mean and standard deviation was calculated for quantitative variables like age, gestational age at presentation, gestational age at delivery, and BMI. Frequency and percentage were calculated for parity and preterm delivery. Results The study involved 160 patients, with the average age in Group A being 29.60±4.9 years and in Group B being 30.96±4.98 years. In terms of gestational age at delivery, Group A had an average of 34.16±1.7 weeks, while Group B had an average of 33.5±1.8 weeks (p-value<0.05). Preterm delivery was observed in 68.5% of Group A and 41.3% of Group B, with a significant p-value of 0.001. The study also discovered that the duration of prolonged pregnancy was significantly higher in Group A compared to Group B, with averages of 14.96±10.37 days and 10.24±8.97 days, respectively (p-value=0.002). Conclusion The results of this study suggest that the combination of sildenafil citrate and nifedipine may offer a promising new approach to improving pregnancy outcomes in cases of PTL. In the present study, sildenafil citrate plus nifedipine showed a significant effect in the management of PTL and prolongation in mean gestational age at delivery.

Ethnic and Gender Diversity in Pathology: A Dream Deferred.

Background Equity, diversity, and inclusion (EDI) remain an elusive dream in the physician workforce in the United States of America (USA). Many studies have documented the tangible and intangible benefits of EDI, including the caregiver, patients, and healthcare organizations. Objective We aim to examine the ethnic and gender diversity trends of the active residents in pathology in United States residency programs. Methods A retrospective cross-sectional study was conducted on the ethnicity and gender distribution of pathology residency trainees from the academic year 2007-2018. The data was compiled from the American Association of Medical Colleges (AAMC) annual report. Data was entered and analyzed using Microsoft Excel 2013 (Microsoft Corporation, Redmond, WA, USA). Frequencies and percentages were calculated, and bar charts and pie charts were used for graphical representation. Results Almost 35,000 US pathology residents were enrolled according to AAMC during this particular period. The highest trend of enrolling in the field of pathology was observed in 2010 and remained the same for years. This shows that the field of pathology in the USA had some acceptance all these years. The most popular speciality in which most residents were enrolled was anatomic/clinical pathology (80%) in which females were dominant over other fields. Conclusion Over the years, we have failed to overcome gender and ethnicity diversity. Gender and ethnicity have a significant influence on leadership positions, academic ranks, and research productivity among pathology faculty members in the USA.

Nusinersen mitigates neuroinflammation in severe spinal muscular atrophy patients.

BACKGROUND: Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, but has not been specifically investigated in patients affected by severe and milder forms of spinal muscular atrophy (SMA). METHODS: In this two-center retrospective study, we investigated signatures of neuroinflammation in forty-eight pediatric male and female SMA1 (n = 18), male and female SMA2 (n = 19), and female SMA3 (n = 11) patients, as well as in a limited number of male and female non-neurological control subjects (n = 4). We employed a Bio-Plex multiplex system based on xMAP technology and performed targeted quantitative analysis of a wide range of pro- and anti-inflammatory cytokines (chemokines, interferons, interleukins, lymphokines and tumor necrosis factors) and neurotrophic factors in the cerebrospinal fluid (CSF) of the study cohort before and after Nusinersen treatment at loading and maintenance stages. RESULTS: We find a significant increase in the levels of several pro-inflammatory cytokines (IL-6, IFN-γ, TNF-α, IL-2, IL-8, IL-12, IL-17, MIP-1α, MCP-1, and Eotaxin) and neurotrophic factors (PDGF-BB and VEGF) in the CSF of SMA1 patients relative to SMA2 and SMA3 individuals, who display levels in the range of controls. We also find that treatment with Nusinersen significantly reduces the CSF levels of some but not all of these neuroinflammatory molecules in SMA1 patients. Conversely, Nusinersen increases the CSF levels of proinflammatory G-CSF, IL-8, MCP-1, MIP-1α, and MIP-1ß in SMA2 patients and decreases those of anti-inflammatory IL-1ra in SMA3 patients. CONCLUSIONS: These findings highlight signatures of neuroinflammation that are specifically associated with severe SMA and the neuro-immunomodulatory effects of Nusinersen therapy.

Spinal muscular atrophy (SMA) is an inherited disorder which leads to muscle weakening. Three therapies have recently been developed, including Nusinersen. However, the effect of SMA on the immune system and how this could be affected by Nusinersen is unknown. The immune system protects the body from infection and, in some disorders, misfunctions and damages the body in the absence of infection. Here, we analyze components of the immune system in body fluids from SMA patients before and after treatment with Nusinersen. The immune system was found to be more active in patients with more severe disease. Treatment with Nusinersen reduced the levels of some, but not all of these, components of the immune system. Thus, treatments that impact the immune system might improve symptoms in patients with SMA.

The role of DNA methylation in progression of neurological disorders and neurodegenerative diseases as well as the prospect of using DNA methylation inhibitors as therapeutic agents for such disorders.

Genome-wide studies related to neurological disorders and neurodegenerative diseases have pointed to the role of epigenetic changes such as DNA methylation, histone modification, and noncoding RNAs. DNA methylation machinery controls the dynamic regulation of methylation patterns in discrete brain regions. Objective: This review aims to describe the role of DNA methylation in inhibiting and progressing neurological and neurodegenerative disorders and therapeutic approaches. Methods: A Systematic search of PubMed, Web of Science, and Cochrane Library was conducted for all qualified studies from 2000 to 2022. Results: For the current need of time, we have focused on the DNA methylation role in neurological and neurodegenerative diseases and the expression of genes involved in neurodegeneration such as Alzheimer's, Depression, and Rett Syndrome. Finally, it appears that the various epigenetic changes do not occur separately and that DNA methylation and histone modification changes occur side by side and affect each other. We focused on the role of modification of DNA methylation in several genes associated with depression (NR3C1, NR3C2, CRHR1, SLC6A4, BDNF, and FKBP5), Rett syndrome (MECP2), Alzheimer's, depression (APP, BACE1, BIN1 or ANK1) and Parkinson's disease (SNCA), as well as the co-occurring modifications to histones and expression of non-coding RNAs. Understanding these epigenetic changes and their interactions will lead to better treatment strategies. Conclusion: This review captures the state of understanding of the epigenetics of neurological and neurodegenerative diseases. With new epigenetic mechanisms and targets undoubtedly on the horizon, pharmacological modulation and regulation of epigenetic processes in the brain holds great promise for therapy.

DNA Methylation and Epigenetic Events Underlying Renal Cell Carcinomas.

Renal cell carcinoma (RCC) refers to a group of tumors that develop from the epithelium of the kidney tubes, including clear cell RCC, papillary RCC, and chromophobe RCC. Most clear cell renal carcinomas have a large histologic subtype, genetic or epigenetic von Hippel-Lindau (VHL). A comprehensive analysis of the genetic modification genome suggested that chromosome 3p loss and chromosome gains 5q and 7 may be significant copy defects in the development of clear RCC. A more potent RCC may develop if chromosome 1p, 4, 9, 13q, or 14q is also lost. Renal carcinogenesis is not associated with chronic inflammation or histological changes. However, if regional hypermethylation of DNA in CpG C-type islands has already accumulated in cancer-free kidney tissue, it implies that the presence of malignant kidney lesions may also be detected by modified DNA methylation. Modification of DNA methylation in cancerous kidney tissue may advance kidney tissue to epigenetic mutations and genes, leading to more serious cancers and even determining a patient's outcome. The genetic and epigenetic profile provides accurate predictors for patients with kidney cancer. New genetic and epigenetic analysis technologies will help to speed up the identification of vital cells for kidney cancer prevention, diagnosis, and treatment.

Immunolocalization of neurokinin 1 receptor in WHO grade 4 astrocytomas, oral squamous cell and urothelial carcinoma.

INTRODUCTION: Neurokinin-1 receptor (NK-1R) induces inflammatory reactions in peripheral tissues but its regulatory effects in target tissues is dependent on receptor signalling. Substance P (SP) has a high affinity for the NK-1R, to which it binds preferentially. We aimed to investigate the expression of NK-1R in World Health Organization (WHO) grade 4 astrocytomas as well as in oral squamous cell carcinoma (OSCC) and urothelial carcinoma, and its association with disease progression. MATERIAL AND METHODS: The study included tissue samples from 19 brain astrocytomas, 40 OSCCs and 10 urothelial carcinomas. NK-1R expression was quantitatively assessed in the tumour cells using immunohistochemistry. The relationship between NK-1R expression in astrocytomas and recurrence-free interval has been explored. RESULTS: The results showed that the NK-1R was intensely expressed in patients with WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. However, cases clinically diagnosed as a low-grade cancer showed reduced NK-1R expression. CONCLUSIONS: NK-1R is overexpressed in all cases of WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. The ubi-quitous presence of SP/NK-1R complex during tumour development and progression suggests a possible therapeutic key strategy to use NK-1R antagonist as an adjuvant therapy in the future.

Accuracy of Classifying Lung Carcinoma Using Immunohistochemical Markers on Limited Biopsy Material: A Two-Center Study.

Introduction Accurate classification of lung cancer into primary and metastatic carcinomas is critical for treatment approaches. Immunohistochemistry (IHC) has always been pivotal in unveiling the diverse cell differentiation lineages present in lung cancer by using specific biomarkers such as TTF1 and p63/p40, which closely reflect the relationship between genotype and phenotype.. Methods A retrospective cross-sectional study was conducted to evaluate 57 Tru-Cut biopsies over two years, from 2020-2022. Tumour morphology was evaluated, and IHC for TTF-1, Napsin A, CK-7, P-63, P-40, and CD-56 was performed in two steps. Results Of the lung cancer cases, 58.5% were adenocarcinoma (ADC), 24.5% were squamous cell carcinoma (SCC), 9.4% were small cell carcinoma, and 7.5% were poorly differentiated carcinoma. TTF1 stain had sensitivity and specificity of 78.9% and 50% in 33 cases of ADC, respectively, while CK7 and Napsin A had 100% sensitivity. P63 stain had 77% sensitivity and 50% specificity in 15 cases of SCC, while P-40 had 100% sensitivity. The CD56 stain was 100% sensitive in five cases of small cell carcinoma. Conclusion IHC staining on small lung biopsies allows accurate sub-classification of poorly differentiated lung cancers; however, there is still significant variability. Surgical resection specimens can be further classified due to architectural features that biopsies lack. Morphological findings would be beneficial in the development of an algorithm for sub-classifying lung carcinoma using a variety of markers.

Comprehensive Analysis of Genes Associated With Sudden Infant Death Syndrome.

Background: Sudden infant death syndrome (SIDS) is a tragic incident which remains a mystery even after post-mortem investigation and thorough researches. Methods: This comprehensive review is based on the genes reported in the molecular autopsy studies conducted on SIDS so far. A total of 20 original studies and 7 case reports were identified and included in this analysis. The genes identified in children or adults were not included. Most of the genes reported in these studies belonged to cardiac channel and cardiomyopathy. Cardiac channel genes in SIDS were scrutinized for further analysis. Results: After screening and removing the duplicates, 42 unique genes were extracted. When the location of these genes was assessed, it was observed that most of these belonged to Chromosomes 11, 1 and 3 in sequential manner. The pathway analysis shows that these genes are involved in the regulation of heart rate, action potential, cardiac muscle cell contraction and heart contraction. The protein-protein interaction network was also very big and highly interactive. SCN5A, CAV3, ALG10B, AKAP9 and many more were mainly found in these cases and were regulated by many transcription factors such as MYOG C2C1 and CBX3 HCT11. Micro RNA, "hsa-miR-133a-3p" was found to be prevalent in the targeted genes. Conclusions: Molecular and computational approaches are a step forward toward exploration of these sad demises. It is so far a new arena but seems promising to dig out the genetic cause of SIDS in the years to come.

Prognostic Significance of Substance P/Neurokinin 1 Receptor and Its Association with Hormonal Receptors in Breast Carcinoma.

Expression and immunolocalization of Substance P (SP)/Neurokinin-1 Receptor (NK-1R) in breast carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/neu, and Ki-67) were evaluated. A cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (grade III), 8 of group B (grade II), and only 3 cases of group C (grade I). All samples were then processed for SP and NK-1R immunohistochemistry for few cases. 14/23 cases (61%) of group A, 7/8 cases (88%) of group B, and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥10% tumor cells), labeled as "+3," was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) cases of group B. Moderate staining labelled as "+2" (in ≥10% tumor cells) was observed in 3/14 (21.4%) cases of group A and 4/8 (50%) cases of group B. Weak positive staining "+1" was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B, and all 2/2 (100%) cases of group C. SP and NK-1R are overexpressed in breast carcinomas, and there is significant association between the grade of tumor and their overexpression.

Enhanced Neurokinin-1 Receptor Expression Is Associated with Human Dental Pulp Inflammation and Pain Severity.

Substance P (SP) is a peptide involved in many biological processes, including nociception and inflammation. SP has a high affinity for its receptor neurokinin-1 (NK-1R). SP/NK-1R complex plays a major role in the interactions going on during the onset of dental pain and inflammation. Objective. To identify the expression of NK-1R in healthy and inflamed human dental pulp, as well as to identify any association with severity of dental pain. Methods. This case-control study included ten irreversibly inflamed samples of dental pulp, which were extirpated from patients presenting with chief complaint of dental pain due to caries. Ten healthy pulps, extirpated from those teeth which were indicated for extraction due to orthodontic reasons, were used as the control group. Visual analog scale (VAS) and modified McGill Pain Questionnaire were used to assess the characteristic and severity of pain. Immunohistochemical study was performed using monoclonal antibodies against NK-1R. Results. The results showed that the NK-1R was expressed intensely in patients with higher pain score. The mean pain score in cases was 7.0 ± 2.0. The healthy dental pulps had negative or mild NK-1R staining of +1 intensity. The NK-1R score in cases was 2.4 ± 0.516 and 0.2 ± 0.4216 in controls. There was significant difference in NK-1R score between both groups (p value <0.05). There was a strong positive correlation between the pain score and NK-1R expression score. As the pain increased, the NK-1R expression score was also increased (0.95∗∗, p value 0.000). Conclusions. NK-1R is overexpressed in inflamed dental pulp. SP/NK-1R modulation may provide a novel approach for the treatment of pulpal inflammation and pain.

Immunohistochemical Expression of the Alpha Nicotinic Acetylcholine Receptor 7 in the Human Normal, Diabetic, and Preeclamptic Placenta and Products of Conception.

Preeclampsia (PE) and gestational diabetes (GD) are complications in advanced pregnancy while miscarriage for early pregnancy. However, the etiological factors are not well understood. Smoking has been associated with these complications as well as the sudden intrauterine deaths, sudden infant death, miscarriages, and still births. However, the immunolocalization of alpha 7 nicotine acetylcholine receptor (α7-nAChR) is not studied. Materials and Methods: α7-nAChR subunit expression was evaluated in 10 paraffin-embedded placental tissues after delivery and 10 tissue samples of products of conception during first trimester by immunohistochemistry. Among the placental tissues, two samples were normal placental tissue, four from PE mother, and four from GD mother. The expression of α7-nAChR was compared between the two groups in general and within the subgroups of placenta as well. Protein expression was evaluated using the nuclear labeling index (%) of villi with positive cells stained, positive cells in the decidua, and intensity of staining in the outer villous trophoblast layer. Results: The expression of α7-nAChR protein was high in all the cases of placenta and products of conception (POCs). α7-nAChR expression showed no notable differences among different cases of miscarriages irrespective of the mother's age and gestational age at which the event occurred. However, there were some changes among the normal, PE, and GD placental groups in the linings of the blood vessels. Changes were restricted to the villi (as opposed to the decidua) lining cells, both cytotrophoblast and syncytiotrophoblast, and were specific to the α7 subunit. PE blood vessel lining was thicker and showed more expression of this receptor in endothelial cells and myofibroblasts in PE and GD groups. In POCs, the strong expression was observed in the decidua myocytes of maternal blood vessels and in syncytiotrophoblast and cytotrophoblast of chronic villi. Conclusion: Nicotine acetyl choline receptors are found to be expressed highly in the placental tissues and in products of conception. They may be associated with the sudden perinatal deaths and miscarriages or complications of pregnancy.

Diagnostic accuracy of carotid intima media thickness by B-mode ultrasonography in coronary artery disease patients.

INTRODUCTION: Cardiovascular diseases (CVD) are the main cause of premature deaths worldwide, and atherosclerosis (AS) is a major risk factor associated with them. B-mode ultrasound is a well-validated research tool that has been translated increasingly into clinical practice. The aim of the study was to assess the diagnostic accuracy of carotid intima media thickness by B-mode ultrasonography in coronary artery disease patients. MATERIAL AND METHODS: This was a case control study, including 100 cases and the same number of controls. Patients with positive angiographic findings and chest pain were considered as cases and those without as negative. Duplex carotid ultrasound was used to detect intima-media thickness (IMT). B-mode real-time ultrasonic images were obtained with a 7 MHz transducer. An intima media thickness of 0.6 mm was considered as being without plaque. RESULTS: The angiographic findings were single-vessel disease, double-vessel disease, and triple-vessel disease in 18%, 11.5%, and 20.5% of cases, respectively, while there were no findings in controls. There was plaque formation in 14.5% and calcification in 12% of the cases. Sensitivity of B-mode ultrasonography was found to be 78%, specificity 75%, positive predictive value 75.72%, and negative predictive value 77.31%. CONCLUSIONS: Carotid ultrasonography can be utilised as a valuable screening tool due to having several advantages, including ease of application, reproducibility, low cost, and strong correlation with atherosclerosis.

Elevated Neurokinin-1 Receptor Expression in Uterine Products of Conception Is Associated With First Trimester Miscarriages.

BACKGROUND: Miscarriage is a common complication of early pregnancy, mostly occurring in the first trimester. However, the etiological factors and prognostic and diagnostic biomarkers are not well known. Neurokinin-1 receptor (NK-1R) is a receptor of tachykinin peptide substance P (SP) and has a role in various pathological conditions, cancers, but its association with miscarriages and significance as a clinicopathological parameter are not studied. Accordingly, the present study aimed to clarify the localization and expression for NK-1R in human retained products of conception (POC). The role of NK-1R is not known in miscarriages. MATERIALS AND METHODS: NK-1R expression was assessed in POC and normal placental tissues by immunohistochemistry. Three- to four-micrometer-thin sections of formalin-fixed paraffin-embedded tissues were used for this purpose. Tissues were processed and then immunohistochemically stained with NK-1R antibody. Brain tissue was used as control for antibody. Protein expression was evaluated using the nuclear labeling index (%). Tissues were counterstained with 3,3'-diaminobenzidine (DAB), and microscopy was performed at 10×, 20×, and 40× magnifications. RESULTS: Ten human POC tissues and 10 normal placental tissues were studied by immunohistochemistry to demonstrate the localization of NK-1R. The expression of NK-1R protein was high in all the cases of both groups. NK-1R expression showed no notable differences among different cases of miscarriages as well as normal deliveries at full term regardless of the mother's age and gestational age at which the event occurred. Statistically, no difference was found in both groups, which is in agreement with our hypothesis and previous findings. CONCLUSION: The expression of NK-1R was similar in all the cases, and it was intense. It shows that dysregulation of NK-1R along with its ligand SP might be involved in miscarriages and also involved in normal delivery. Our results provide fundamental data regarding this anti-NK-1R strategy. Thus, the present study recommends that SP/NK-1R system might, therefore, be considered as an emerging and promising diagnostic and therapeutic strategy against miscarriages. Hence, we report for the first time the expression and localization of NK-1R in POC. We suggest NK-1R antagonist in addition to the immunoglobulins and human chorionic gonadotropin to diagnose and treat spontaneous miscarriages.