Significance of vitamin D responsiveness on the etiology of vitamin D-related diseases.

Vitamin D resistance (VDRES) explains the necessity for higher doses of Vitamin D (VD) than those recommended for treatment success. VD receptor (VDR) signaling blockade, such as that caused by infections and poisons, is one basis for VDRES etiology. Mutations within genes affecting the VD system cause susceptibility to developing low VD responsiveness and autoimmunity. In contrast, VD hypersensitivity (VDHY) occurs if there is extra VD in the body; for example, as a result of an overdose of a VD supplement. Excess 1,25(OH)2D3 is produced in lymphomas and granulomatous diseases. The placenta produces excess 1,25(OH)2D3. Gene mutations regulating the production or degradation of 1,25(OH)2D3 enhance the effects of 1,25(OH)2D3. Increased 1,25(OH)2D3 levels stimulate calcium absorption in the gut, leading to hypercalcemia. Hypercalcemia can result in the calcification of the kidneys, circulatory system, or placenta, leading to kidney failure, cardiovascular disease, and pregnancy complications. The primary treatment involves avoiding exposure to the sun and VD supplements. The prevalence rates of VDRES and VDHY remain unclear. One estimate was that 25%, 51%, and 24% of the patients had strong, medium, and poor responses, respectively. Heavy-dose VD therapy may be a promising method for the treatment of autoimmune diseases; however, assessing its potential side effects is essential. To avoid VD-mediated hypercalcemia, responsiveness must be considered when treating pregnancies or cardiovascular diseases associated with VD. Furthermore, how VD is associated with the related disorders remains unclear. Investigating responsiveness to VD may provide more accurate results.

Immediate effects of urgent reorganisation of emergency department-based treatment pathway in nonperforated appendicitis: a retrospective study.

BACKGROUND: Acute appendicitis is a global disease and a very common indication for emergency surgery worldwide. The need for hospital resources is therefore constantly high. The administration in Kanta-Häme Central Hospital, Southern Finland, called for an urgent reorganisation due to shortage of hospital beds at the department of general surgery. Postoperative treatment pathway of patients with nonperforated acute appendicitis was ordered to take place in the Emergency Department (ED). The aim of this study was to assess, whether this reorganisation was feasible and safe, i.e. did it affect the length of in-hospital stay (LOS) and the 30-day complication rate. METHODS: This is a retrospective pre- and post-intervention analysis. After the reorganisation, most patients with nonperforated appendicitis were followed postoperatively at the 24-h observation unit of the ED instead of surgical ward. Patients operated during the first 3 months after the reorganisation were compared to those operated during the 3 months before it. A case met inclusion criteria if there were no signs of appendiceal perforation during surgery. Exclusion criteria comprised age < 18 years and perforated disease. RESULTS: Appendicectomy was performed on 112 patients, of whom 62 were adults with nonperforated appendicitis. Twenty-seven of the included patients were treated before the reorganisation, and 35 after it. Twenty of the latter were followed only at the ED. Postoperative LOS decreased significantly after the reorganisation. Median postoperative time till discharge was 15.7 h for all patients after the reorganisation compared to 24.4 h before the reorganisation (standard error 6.2 h, 95% confidence interval 2.3-15.2 h, p < 0.01). There were no more complications in the group treated postoperatively in the ED. CONCLUSIONS: Early discharge of patients with nonperforated appendicitis after enforced urgent reorganisation of the treatment pathway in the ED observation unit is safe and feasible. Shifting the postoperative monitoring and the discharge policy of such patients to the ED - instead of the surgical ward - occurred in the majority of the cases after the reorganisation. This change may spare resources as in our series it resulted in a significantly shorter LOS without any increase in the 30-day complication rate.

Aberrant nest building and prolactin secretion in vitamin D receptor mutant mice.

1Alpha,25(OH)2D3, the hormonal form of vitamin D, is a neuroactive seco-steroid hormone with multiple functions in the brain. Most of these effects are mediated through the nuclear vitamin D receptor (VDR), widely distributed in the central nervous system. Our earlier studies showed that mutant mice lacking functional VDR have specific behavioural abnormalities, including anxiety and aberrant maternal behaviour, which may be hormonally regulated. Here we describe impaired nest building behaviour in VDR mutant mice. Since prolactin plays a key role in the regulation of nest building in both sexes, we also examine whether VDR mutant mice have altered prolactin levels. Overall, serum prolactin levels were increased in VDR mutant mice, accompanied by marked impairments in their nest building activity. In contrast, there were no differences in prolactin mRNA expression levels between wildtype control mice and VDR mutant mice. Collectively, these data suggest that partial genetic ablation of VDR affects prolactin system in mice, and that altered serum prolactin levels in VDR mutants may underlie some of their behavioural abnormalities, such as impaired nest building.