Progression of Mineral Ion Abnormalities in Patients With Jansen Metaphyseal Chondrodysplasia

Context: Five different activating PTH/PTH-related peptide (PTHrP) receptor (PTHR1) mutations have been reported as causes of Jansen metaphyseal chondrodysplasia (JMC), a rare disorder characterized by severe growth plate abnormalities and PTH-independent hypercalcemia. / Objectives: Assess the natural history of clinical and laboratory findings in 24 patients with JMC and characterize the disease-causing mutant receptors in vitro. / Patients and Methods: The H223R mutation occurred in 18 patients. T410P, I458R and I458K each occurred in single cases; T410R was present in a father and his two sons. Laboratory records were analyzed individually and in aggregate. / Results: Postnatal calcium levels were normal in most patients, but elevated between 0.15 and 10 years (11.8 ± 1.37 mg/dL) and tended to normalize in adults (10.0 ± 1.03 mg/dL). Mean phosphate levels were at the lower end of the age-specific normal ranges. Urinary calcium/creatinine (mg/mg) were consistently elevated (children, 0.80 ± 0.40; adults, 0.28 ± 0.19). Adult heights were well below the 3rd percentile for all patients, except for those with the T410R mutation. Most patients with JMC had undergone orthopedic surgical procedures, most had nephrocalcinosis, and two had advanced chronic kidney disease. The five PTHR1 mutants showed varying degrees of constitutive and PTH-stimulated cAMP signaling activity when expressed in HEK293 reporter cells. The inverse agonist [L11,dW12,W23,Y36]PTHrP(7–36) reduced basal cAMP signaling for each PTHR1 mutant. / Conclusions: Except for T410R, the other PTHR1 mutations were associated with indistinguishable mineral ion abnormalities and cause similarly severe growth impairment. Hypercalciuria persisted into adulthood. An inverse agonist ligand effectively reduced in vitro PTH-independent cAMP formation at all five PTHR1 mutants, suggesting a potential path toward therapy

A novel de novo androgen receptor nonsense mutation in a sex-reversed 46,XY infant

10.1038/s41439-021-00167-5Human Genome Variation8135

Double sarcomatoid carcinomas of the oesophagus

Sarcomatoid carcinoma of the oesophagus is uncommon. A case of double sarcomatoid carcinomas was identified in the oesophagus of a 48-year-old man. This is the fourth case of multiple primary sarcomatoid carcinomas of the oesophagus and the first case with detailed pathological features presented. The clinicopathological features of multiple primary tumours and sarcomatoid carcinoma of the oesophagus are also reviewed.link_to_subscribed_fulltex

Double sarcomatoid carcinomas of the oesophagus

Sarcomatoid carcinoma of the oesophagus is uncommon. A case of double sarcomatoid carcinomas was identified in the oesophagus of a 48-year-old man. This is the fourth case of multiple primary sarcomatoid carcinomas of the oesophagus and the first case with detailed pathological features presented. The clinicopathological features of multiple primary tumours and sarcomatoid carcinoma of the oesophagus are also reviewed.link_to_subscribed_fulltex

Evaluating seaweed farming as an eco-engineering strategy for ‘blue’ shoreline infrastructure

Ecological Engineerin

Small cell carcinoma of the esophagus

Background. Small cell carcinoma of the esophagus is regarded as having a poor prognosis with frequent systemic dissemination. Methods. A review of the records and histologic sections of 11 patients with primary small cell carcinoma of the esophagus seen in 11 years was undertaken. They were analyzed and compared with the more common squamous cell carcinomas and adenocarcinomas. Results. Small cell carcinoma of the esophagus constituted 1% of all esophageal tumors and was mainly located at the middle and lower thirds (90%) of the esophagus. Primary treatment consisted of tumor resection in five patients (46%), chemotherapy and radiotherapy in two (18%); surgical bypass in one (9%), radiotherapy after exploratory laparotomy in one (9%), intubation in one (9%), and no active intervention in one (9%). Two of the five resected tumors were Stage IIB disease, and three were Stage III disease. Five of the six patients in the non-resection group had distant metastases at presentation (45% of all patients). The median survival of patients who had chemotherapy (three of whom also had radiotherapy) was 16.7 months (range, 2.8-72 months) and was 2.2 months (range, 4 days to 9.1 months) for those with no chemotherapy. The overall median survival was 3.1 months for all patients. The prognosis was not significantly different from those with squamous cell carcinomas or adenocarcinomas. Conclusions. Small cell carcinoma of the esophagus should be regarded as a systemic disease, and multimodality treatment, including chemotherapy, should be used. Surgery may be offered in selected patients to manage local disease as part of a chemotherapy-based treatment program.link_to_subscribed_fulltex

Correlation Between Lipoprotein-Related Phospholipase A2 and Metabolic Syndrome

Kai-Yu Wang,1 Yi-Chuan Chen,1,2 Jau-Yuan Chen,1,2 Song-Seng Loke,3 Wei-Chung Yeh,4 Wen-Cheng Li1,2,5 1Department of Family Medicine, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Family Medicine, Chang-Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan; 4Department of Family Medicine, Chang-Gung Memorial Hospital at Keelung, Keelung, Taiwan; 5Department of Health Management, Xiamen Chang-Gung Hospital, Xiamen, People’s Republic of ChinaCorrespondence: Wen-Cheng Li, Email [email protected]: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been recognized as a valuable biomarker for identifying the risk of cardiovascular diseases and inflammation. Furthermore, there is strong evidence to suggest that metabolic syndrome is closely associated with chronic inflammation. Accordingly, the present study endeavors to examine the potential correlation between metabolic syndrome and the levels of Lp-PLA2.Methods: To explore the relationship between Lp-PLA2 levels and metabolic syndrome, and to establish the predictive cut-off value of Lp-PLA2, a retrospective analysis was conducted using medical data from a sample of 3549 Chinese adults (comprising 2182 men and 1367 women) aged between 18 and 50 years, who had undergone health check-ups. In addition, the study also sought to investigate any potential differences in Lp-PLA2 levels based on sex and age.Results: The analysis of the data indicated that participants had a mean age of 44.2 years, a mean Lp-PLA2 level of 589 IU/L, and a metabolic syndrome prevalence of 22%. Lp-PLA2 levels were significantly different between males and females, and a significant correlation was observed between Lp-PLA2 levels and clinical and metabolic characteristics, including BMI, cholesterol, and triglycerides. Interestingly, Lp-PLA2 demonstrated potential as an indicator of metabolic syndrome, particularly in females, despite other biomarkers, such as TG/HDL-C and WHR, exhibiting better area under the curve.Conclusion: Our findings suggest that Lp-PLA2 may serve as a useful biomarker for identifying individuals at risk of developing metabolic syndrome, particularly in females. Further research is needed to explore the potential of Lp-PLA2 as a diagnostic and therapeutic target for metabolic syndrome.Keywords: Lp-PLA2, lipoprotein, metabolic syndrome, cardiovascular risk, and lipid profil