Adiponectin rs1501299 and chemerin rs17173608 gene polymorphism in children with type 1 diabetes mellitus: relation with macroangiopathy and peripheral artery disease.

AIM: Although macrovascular complications represent the leading cause of mortality in type 1 diabetes mellitus (T1DM), the prevalence of subtle macrovascular affection including peripheral artery disease (PAD) among children with T1DM and its genetic predictors remains to be unraveled. Increasing evidence suggests a link between adiponectin rs1501299 and chemerin rs17173608 gene polymorphism and atherogenesis, and insulin resistance. Hence, this study assess the prevalence of these variants among children with T1DM in comparison to healthy controls and their association with macrovascular complications, namely PAD and hyperlipidemia. METHODS: Fifty children with T1DM and 50 matched controls underwent a thorough assessment including adiponectin rs1501299 and chemerin rs17173608 gene polymorphisms, fasting lipids, glycated hemoglobin (HbA1c), and ankle-brachial index (ABI). Cochran-Armitage trend test was used to decide the risk allele and evaluate the association between the candidate variant and PAD using a case-control design. RESULTS: Children with T1DM were found to have significantly higher ABI (p = 0.011) than controls. Chemerin gene polymorphism was detected in 41 children with T1DM (82.0%), while adiponectin gene polymorphism was detected in 19 children (38.0%). Children with T1DM having GG chemerin variant and those having TT adiponectin variant had significantly higher cholesterol with significantly lower HDL-C and ABI than those having the other two variants (p < 0.005). Children with T1DM having abnormal ABI had significantly higher chemerin G (p = 0.017) and adiponectin T (p = 0.022) alleles than those with normal ABI. Cholesterol and ABI were independently associated with chemerin and adiponectin gene polymorphism by multivariable regression analysis. CONCLUSION: Children with T1DM having chemerin and adiponectin gene polymorphisms have significantly higher cholesterol and ABI than those without these polymorphisms and controls. TRIAL REGISTRATION: The Research Ethics Committee of Ain Shams University, approval number R 31/2021.

Cutaneous Malignant Melanoma Presenting as an Isolated Splenic Metastasis: An Update.

Although the spleen is a highly vascularized organ, metastatic deposits from non-hematolymphoid solid malignancies are rare. This is reasoned to the inherent resistance of the splenic parenchyma to harbor metastases. The splenic capsule, lack of afferent lymphatics, contractile properties of the spleen, and the angular and gyroid course of the splenic artery form several barriers against the metastatic spread of malignant tumors. Moreover, the immune cells in the white and red pulps of the spleen have strong defensive ability against the tumor cells. Metastasis from solid tumors to the spleen often occurs only during widespread distant spread. Malignant melanoma is a rare but fatal malignancy. Isolated splenic metastasis from malignant melanoma is exceptionally rare. Studies that addressed the splenic metastasis from cutaneous malignant melanoma are scarce. This minireview was performed to address this subject. Here we present an overview of the clinicopathologic features of isolated splenic metastatic melanoma. The diagnostic biochemical markers in melanoma are also discussed.

An Unusual Solitary Fibrous Tumor of the Ischiorectal Region.

Solitary fibrous tumors (SFTs) are rare fibroblastic/myofibroblastic proliferations that occur in a wide range of anatomical sites. These tumors have nonspecific clinical presentations often with unpredictable biological behavior. SFTs can be slow growing low-risk tumors or rapidly growing high-risk tumors. They show a wide variety of histological features and typically are characterized by NAB2-STAT6 fusion. SFTs of the ischiorectal fossa are rare, with few studies reported in the literature to date. Here, we report a 90-year-old male who had a road traffic accident in October 2018. A pelvic computed tomography (CT) revealed a mass measuring 3.5 × 2.5 cm in the right ischiorectal fossa. Histopathology of the CT-guided biopsies confirmed the diagnosis of low-grade SFT. No surgical intervention was needed since the patient was asymptomatic. In January 2022, a follow-up CT showed a gradual increase in tumor size (5 × 3.5 × 3 cm), but not infiltrating the surrounding structures. However, the patient complained of constipation, which warranted a surgical excision of the mass. Subsequently, immunohistological examination reconfirmed the diagnosis of low-risk SFT. Here, we discussed the clinicopathological features of the case and the relevant literature about pelvic SFTs. In conclusion, SFTs should be considered in the differential diagnosis of any ischiorectal mass. It is recommended that tissue samples be obtained, and immunohistology should be performed.

Genotypic spectrum of 21-hydroxylase deficiency in an endogamous population.

BACKGROUND: Congenital adrenal hyperplasia (CAH) due to autosomal recessive 21-hydroxylase deficiency (21-OHD) is caused by defects in the CYP21 (CYP21A2) gene. Several mutations have been identified in the CYP21 (CYP21A2) gene of patients with 21-OHD. We aimed at determining the frequency of these mutations among a group of Egyptian patients and studying the genotype-phenotype correlation. METHODS: Forty-seven patients with CAH due to 21-OHD from 42 different families diagnosed by clinical and hormonal evaluation and classified accordingly into salt wasting (SW) and simple virilizing (SV) phenotypes were enrolled. Their ages ranged between 1.78 and 18.99 years. Molecular analysis of the CYP21 (CYP21A2) gene was performed for the detection of eleven common mutations: P30L, I2 splice (I2 G), Del 8 bp E3 (G110del8nt), I172N, cluster E6 (I236N, V237E, M239K), V281L, L307 frameshift (F306 + T), Q318X, R356W, P453S, R483P by polymerase chain reaction (PCR) and reverse hybridization. RESULTS: Disease-causing mutations were identified in 47 patients, 55.31% of them were compound heterozygous. The most frequent mutations were I2 splice (25.43%), followed by cluster E6 (16.66%) and P30L (15.78%). Two point mutations (P453S, R483P) were not identified in any patient. In the SW patients, genotypes were more compatible with their phenotypes. CONCLUSION: Molecular characterization should be considered along with clinical and biochemical diagnosis of CAH since it could confirm the diagnosis, outline the treatment strategy and morbidity, and ensure proper genetic counseling.

Challenge in the Pathological Diagnosis of the Follicular- Patterned Thyroid Lesions.

BACKGROUND: The follicular-patterned thyroid lesions (FPTLs) include hyperplastic nodules (HN), follicular adenoma (FA), non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP), follicular carcinoma (FC), and the follicular variant of papillary carcinoma (FVPTC). Sometimes the pathologists cannot accurately separate these lesions from each others on a histological basis. AIMS: To evaluate the utility of immunohistochemistry in the diagnosis of FPTLs. MATERIALS AND METHODS: Immunohistochemical analysis, incorporating 83 cases of histologically confirmed FPTLs out of which 20 carcinomas, 51 benign FPTLs (38 HN and 13 FA), and 12NIFTP were separated from each others using four immunostains (HBME-1, CK19, Galectin-3, and CD56). RESULTS: We found statistically significantly more frequent expression of HBME-1, CK19, Galectin-3 proteins in carcinomas as compared to benign FPTLs (p = <0.01). HBME-1 and Galectin-3 were the most sensitive markers for the diagnosis of malignant FPTLs (75%). Galectin-3 was the most specific marker for the diagnosis of carcinoma (90.3%). CONCLUSIONS: The histomorphological features remain the cornerstone of the diagnosis of FPTN. Although HBME-1, Galectin-3, and CK19 immunostains have some diagnostic value in the separation of malignant from benign FPTLs, they are variably expressed in the benign and malignant FPTLs. No single immunostain has sufficient sensitivity and specificity and therefore their diagnostic use is controversial. Future studies are mandated to find more reliable markers that can separate between benign and malignant FPTLs.

Primary Basidiobolomycosis of the Cecum in Immunocompetent Patients: Two Case Reports.

Colonic basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum. Primary cecal basidiobolomycosis is an exceptionally rare condition. The study describes two cases of primary basidiobolomycosis of the cecum in immunocompetent male and female patients (one each). The patients presented with fever, abdominal pain, weight loss, eosinophilia, and high erythrocyte sedimentation rates. Computed tomography revealed wall thickening and mass lesions involving the cecum, suggesting malignancy. Right hemicolectomies were performed to relieve the intestinal obstruction. On microscopy, there were destructive, transmural eosinophil-rich pyogranulomatous reactions with thin-walled, pauci-septated fungal elements surrounded by Splendore-Hoeppli bodies. The patients received antifungal drugs, with no evidence of dissemination or recurrence on follow-up. Primary cecal basidiobolomycosis in immunocompetent hosts is a rare occurrence. It oftentimes clinically masquerades malignant neoplasms and therefore its identification mandates its inclusion in the differential diagnosis of a colonic mass, equally both on the part of the clinicians and pathologists.

Transmembrane and Tetratricopeptide Repeat Containing 4 Is a Novel Diagnostic Marker for Prostate Cancer with High Specificity and Sensitivity.

The histopathologic diagnosis of prostate cancer (PCa) from biopsies is a current challenge if double or triple staining is needed. Therefore, there is an urgent need for development of a new reliable biomarker to diagnose PCa patients. We aimed to explore and compare the expression of TMTC4 in PCa cells and tissue specimens and evaluate its sensitivity and specificity. The expression of TMTC4 in PCa and normal prostate epithelial cells was determined by real-time PCR and Western blot analyses. Immunohistochemical (IHC) staining of TMTC4 was performed on tissues collected from PCa and benign prostatic hyperplasia (BPH). Our results show a high expression of TMTC4 on mRNA and protein levels in PCa versus BPH1 and normal cells (p < 0.05). IHC results show strong cytoplasmic expressions in PCa cases (p < 0.001) as compared to BPH cases. The overall accuracy as measured by the AUC was 1.0 (p < 0.001). The sensitivity and specificity of the protein were 100% and 96.6%, respectively. Taken together, we report a high TMTC4 expression in PCa cells and tissues and its ability to differentiate between PCa and BPH with high sensitivity and specificity. This finding can be carried over to clinical practice after its confirmation by further studies.

Incidence of Gastrointestinal Neuroendocrine Tumor: Case Series, Armed Forces Hospital Southern Region, Hospital-Based Tumor Board Registry.

Neuroendocrine tumors are aggressive and rare tumors which can occur almost everywhere in the body. The annual incidence of neuroendocrine tumors is 2.5-5 per 100000. We report seven cases of gastrointestinal neuroendocrine tumors which were diagnosed and treated at our hospital from the time period of 2016-2018 knowing that the total number of our hospital tumor board cases registry during the same period was 444 cases.

Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis- and autophagy-associated molecules.

In clinical medicine, indomethacin (IND, a non-steroidal anti-inflammatory drug) is used variously in the treatment of severe osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. A common complication found alongside the therapeutic characteristics is gastric mucosal damage. This complication is mediated through apoptosis and autophagy of the gastrointestinal mucosal epithelium. Apoptosis and autophagy are critical homeostatic pathways catalysed by caspases downstream of the gastrointestinal mucosal epithelial injury. Both act through molecular signalling pathways characterized by the initiation, mediation, execution and regulation of the cell regulatory cycle. In this study we hypothesized that dysregulated apoptosis and autophagy are associated with IND-induced gastric damage. We examined the spectra of in vivo experimental gastric ulcers in male Sprague-Dawley rats through gastric gavage of IND. Following an 18-hour fast, IND was administered to experimental rats. They were sacrificed at 3-, 6- and 12-hour intervals. Parietal cells (H+ , K+ -ATPase ß-subunit assay) and apoptosis (TUNEL assay) were determined. The expression of apoptosis-signalling caspase (caspases 3, 8, 9 and 12), DNA damage (anti-phospho-histone H2A.X) and autophagy (MAP-LC3, LAMP-1 and cathepsin B)-related molecules in gastric mucosal cells was examined. The administration of IND was associated with gastric mucosal erosions and ulcerations mainly involving the gastric parietal cells (PCs) of the isthmic and upper neck regions and a time-dependent gradual increase in the number of apoptotic PCs with the induction of both apoptotic (upregulation of caspases 3 and 8) cell death and autophagic (MAP-LC3-II, LAMP-1 and cathepsin B) cell death. Autophagy induced by fasting and IND 3 hours initially prompted the degradation of caspase 8. After 6 and 12 hours, damping down of autophagic activity occurred, resulting in the upregulation of active caspase 8 and its nuclear translocation. In conclusion we report that IND can induce time-dependent apoptotic and autophagic cell death of PCs. Our study provides the first indication of the interactions between these two homeostatic pathways in this context.

EXHANCE-3: a cohort study of the exhalation delivery system with fluticasone for chronic sinusitis with or without nasal polyps.

BACKGROUND: Inhaled nasal corticosteroid sprays (INS) are often inadequate to treat chronic rhinosinusitis (CRS). The exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) may improve outcomes in CRS by increasing medication delivery to target superior/posterior anatomic sites. This study assessed safety and efficacy of EDS-FLU in a large population with moderate-to-severe CRS with or without nasal polyps (CRSwNP, CRSsNP). METHODS: Prospective, multicenter, 12-week, single-arm study of EDS-FLU 372 Â#181;g twice daily (BID) at 38 U.S. sites. Safety was assessed by adverse-event evaluations, nasal endoscopy, and ocular examinations. Efficacy was serially assessed by outcomes including nasal endoscopy (Lund-Kennedy Score, polyp grade), patient- and physician-reported outcomes (22-item Sinonasal Outcome Test [SNOT-22]), study-defined surgical indicator assessment, and Patient Global Impression of Change (PGIC). RESULTS: 705 comparatively refractory subjects were enrolled, 603 CRSsNP and 102 CRSwNP [moderate-to-severely symptomatic; baseline SNOT-22 ~43, high rates of prior INS use (92.3%) and/or prior surgery (27.5%)]. More than 90% reported improvement on treatment by PGIC. SNOT-22 scores improved substantially and similarly in patients with NP (-23.7) and without NP (-24.4). Among patients with baseline Lund-Kennedy edema scores >0, 33.3% (CRSwNP) and 54.8% (CRSsNP) had complete resolution of edema. In CRSwNP patients, 48% had polyp elimination in ?1 nostril, 63% had ?1-point improvement in polyp grade, mean bilateral polyp grade decreased from 2.9 to 1.6, and study-defined surgical eligibility decreased. EDS-FLU was generally well tolerated, with a safety profile similar to conventional INS sprays when used to treat CRS CONCLUSION: EDS-FLU 372 #181;g BID in the treatment of CRS with or without polyps was safe, well-tolerated, and produced substantial improvement across a broad range of both objective and subjective measures.

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

Gastric metastases from invasive primary mucosal epithelioid malignant melanoma of the hard palate: report of the first case in the English literature.

Melanocytes arise from the neural crest and migrate to the epidermis, meninges, uveal tract and ectodermal mucosa. Normal gastric mucosa lacks melanocytes. A 64-year-old woman presented to us with nausea and vomiting. She had a past history of invasive primary mucosal epithelioid malignant melanoma of the hard palate 21 months ago, treated by a wide surgical excision. Gastroscopy revealed multiple punched out ulcers involving the stomach and the first part of duodenum. Immunohistology and clinicopathologic correlation established the diagnosis of metastatic gastric malignant melanoma. To our knowledge, this is the first report in the English literature about gastric metastases arising from primary palatal mucosal melanoma.

Multiple drug resistance and strength of attachment to surfaces in Pseudomonas aeruginosa isolates.

AIMS: To investigate the presence of a relationship between the strength of attachment of Pseudomonas aeruginosa to stainless steel surfaces and their observed multiple drug resistance. METHODS AND RESULTS: Multiple drug resistance of clinical and environmental isolates of Ps. aeruginosa was evaluated using disc diffusion method. The blot succession technique was used to quantify the strength of attachment of Ps. aeruginosa isolates. Different multiple drug-resistant Ps. aeruginosa isolates exhibited variable attachment strength. Although the highest multiple drug-resistant clinical isolate was shown to have the least attachment strength among clinical isolates, a weak correlation was found between attachment strength and multiple resistance among our investigated Ps. aeruginosa isolates. CONCLUSIONS: There is a weak correlation between multiple drug resistance and strength of attachment to stainless steel surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: Even low-resistant Ps. aeruginosa could have the potential of attaching firmly to surfaces and forming biofilm.

Relationship between endotracheal tube leakage and under-reading of tidal volume in neonatal ventilators.

AIM: Protective ventilation in neonates requires careful volume monitoring to prevent ventilator-induced lung injury caused by baro/volutrauma and hence chronic lung disease. This study investigated the effect of endotracheal tube (ET) leakage on the displayed tidal volume using an in vitro model. METHODS: A neonatal lung model was ventilated via a 3 mm ET using three ventilators [Babylog 8000 (BL), Leoni (LE) and Stephanie (ST)]. Tidal volume was measured by each ventilator at the Y-piece and by a pneumotach (CO(2)SMO(+)) in the model. ET leaks were simulated by open tubes of different lengths. PIP (20 cmH(2)O) and PEEP (5 cmH(2)O) were kept constant, and the respiratory rate (RR) was varied between 20/min and 70/min (Ti:Te = 1:1). RESULTS: Tidal volume displayed by a ventilator decreased independently of RR with increasing leakage up to 21% (BL), 30% (LE) and 33% (ST). However, the volume delivered to the lung was nearly constant. The displayed leakage varied between 0 and 78% and was dependent on RR and leakage resistance. There were distinct differences between the three ventilators in the relationship between displayed leakage and volume error. Accepting a volume error <10% for RR between 20 and 70/min, ET leakage of up to 20% for BL, 12% for LE, but only <5% for ST, was acceptable. CONCLUSION: Tidal volume underestimation arising from ET leakage depends on ventilator pressures, timing parameters and ventilator-specific algorithms for signal processing. Therefore, neonatologists should be aware of these issues to prevent lung over-inflation when adjusting target volume in the presence of ET leakage.

Cost-effective syphilis screening in military recruit applicants.

A cost-effectiveness analysis of syphilis screening was performed. Strategies included no screening, universal testing at military entrance processing stations, universal testing at basic training centers, and contracting centralized screening. Probabilities derived from data retained on recruit applicants from 1989 through 1991 (N = 1,588,143) and from the published literature were used. Cost estimates were derived from costs incurred by the military and costs projected from implementing new strategies. Sensitivity analyses were performed. Modifying the existing contract for human immunodeficiency virus screening to include syphilis screening would maximize the effectiveness of screening at a cost to the Department of Defense of $9.52 per additional year of service received. The no-screening option was significantly more cost-saving than the current method of testing. Syphilis is rare and treatable, and individuals with syphilis will be identified by other means in many cases. Syphilis screening of recruit applicants at the military entrance processing stations should cease, saving the military $2,541,000 per year.

Reducing medical attrition: the role of the Accession Medical Standards Analysis and Research Activity.

This paper illustrates how adding an epidemiologic perspective to medical accession policy development allows the Department of Defense to address unacceptably high rates of premature attrition, lost duty time, avoidable medical care costs, sick leave, disability, and various wasteful, inefficient practices. The Accession Medical Standards Analysis and Research Activity is a major new epidemiologic entity. Historically, military medical accession policy and waiver deliberations were based heavily on expert opinion. A common limitation of expert opinion is that although experience teaches much about individuals with certain conditions who develop problems, it does not teach about individuals with the same conditions who remain well. The Accession Medical Standards Analysis and Research Activity produces the analyses of epidemiologic data necessary for the joint personnel and medical flag-level Department of Defense Accessions Medical Standards Steering Committee to make evidence-based accession policy decisions.

pH-metric studies on ternary metal complexes of some amino acids and benzimidazole.

The stability constants of binary and ternary complexes of copper(II) and nickel(II) with some amino acids (d-histidine, dl-serine, lysine) as primary ligands and benzimidazole as a secondary ligand were determined pH-metrically. The study was conducted in 10% (v/v) ethanol-H(2)O medium and at an ionic strength of 0.1 mol dm(-3) NaNO(3) at 20 +/- 1 degrees C, Values of Delta log K were discussed on the basis of statistical considerations and the nature of the species formed. The stability of the binary and mixed ligand complexes are discussed in terms of the molecular structure of benzimidazole and the amino acids as well as the nature of the metal ion.