Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults

Ketogenic diets (KDs) often contain high levels of saturated fat, which may increase liver fat, but the lower carbohydrate intake may have the opposite effect. Using a controlled feeding design, we compared liver fat responses to a hypocaloric KD with a placebo (PL) versus an energy-matched low-fat diet (LFD) in overweight adults. We also examined the added effect of a ketone supplement (KS). Overweight adults were randomized to a 6-week KD (KD + PL) or a KD with KS (KD + KS); an LFD group was recruited separately. All diets were estimated to provide 75% of energy expenditure. Weight loss was similar between groups (p > 0.05). Liver fat assessed by magnetic resonance imaging decreased after 6 week (p = 0.004) with no group differences (p > 0.05). A subset with nonalcoholic fatty liver disease (NAFLD) (liver fat > 5%, n = 12) showed a greater reduction in liver fat, but no group differences. In KD participants with NAFLD, 92% of the variability in change in liver fat was explained by baseline liver fat (p < 0.001). A short-term hypocaloric KD high in saturated fat does not adversely impact liver health and is not impacted by exogenous ketones. Hypocaloric low-fat and KDs can both be used in the short-term to significantly reduce liver fat in individuals with NAFLD.     

Effects of Combined Vitamin K2 and Vitamin D3 Supplementation on Na[18F]F PET/MRI in Patients with Carotid Artery Disease: The INTRICATE Rationale and Trial Design

INTRICATE is a prospective double-blind placebo-controlled feasibility study, assessing the influence of combined vitamin K2 and vitamin D3 supplementation on micro-calcification in carotid artery disease as imaged by hybrid Sodium [¹⁸F]Fluoride (Na[¹⁸F]F) positron emission tomography (PET)/ magnetic resonance imaging (MRI). Arterial calcification is an actively regulated process and results from the imbalance between calcification promoting and inhibiting factors. Considering the recent advancements in medical imaging, ultrasound (US), PET/MRI, and computed tomography (CT) can be used for the selection and stratification of patients with atherosclerosis. Fifty-two subjects with asymptomatic carotid artery disease on at least one side of the neck will be included in the study. At baseline, an Na[¹⁸F]F PET/MRI and CT examination will be performed. Afterwards, subjects will be randomized (1:1) to a vitamin K (400 µg MK-7/day) and vitamin D3 (80 µg/day) or to placebo. At the 3-month follow-up, subjects will undergo a second Na[¹⁸F]F PET/MRI and CT scan. The primary endpoint is the change in Na[¹⁸F]F PET/MRI (baseline vs. after 3 months) in the treatment group as compared to the placebo arm. Secondary endpoints are changes in plaque composition and in blood-biomarkers. The INTRICATE trial bears the potential to open novel avenues for future large scale randomized controlled trials to intervene in the plaque development and micro-calcification progression.     

The Correlation Between the New Rigiscan Plus Software and the Final Diagnosis in the Evaluation of Erectile Dysfunction

Purpose

The computer generated recordings for 2 nights in 40 patients studied with the RigiScan^† device were reevaluated using the new RigiScan Plus software to test its value in improving the discrimination between psychogenic and organic erectile dysfunction.

Materials and Methods

Each man was evaluated for erectile dysfunction with a detailed medical and sexual history, physical examination, biothesiometry, plethysmography, 2 nights of ambulatory RigiScan monitoring and a psychological evaluation that usually included a private interview with the sexual partner. At the conclusion of evaluation each patient was broadly classified as having organic or psychogenic erectile dysfunction. The RigiScan reports were initially independently analyzed without the investigator's knowledge of the final diagnosis by determining the single best erectile event, with a minimal cutoff value of 60 percent erection for 5 minutes as necessary to be considered normal and the sum of measurements from the 2 nights. The original reading and final diagnosis were correlated. At this point the data were processed with the new RigiScan Plus software using 2 new measurements: 1) rigidity activity units and 2) tumescence activity units at the base and tip of the penis, and the results were correlated with the final diagnosis.

Results

Evaluation of the single best event again showed that tip rigidity was the best single predictor if the diagnostic criteria were modified to 70 percent tip rigidity for 5 minutes with an estimate of correct classification of 92.5 percent. Nearly the same accuracy was obtained by base single event rigidity, tip rigidity and base tumescence activity units (each 90 percent). The summary analysis of all erectile events during the 2 nights of evaluation that had a low correlation with the final diagnosis using the original software showed that the best overall predictor of final diagnosis was tip tumescence activity units (92.5 percent), followed by base rigidity and tumescence activity units (each 90 percent).

Conclusions

The RigiScan Plus software introduced 4 new parameters that facilitate interpretation of the RigiScan data. The new software did not improve the correlation with the final diagnosis compared to the subjective single best event analysis but added new objective parameters, measured and displayed by the software, that facilitate use of the data by the physician.     

Superior mesenteric artery first approach versus standard pancreaticoduodenectomy:a systematic review and meta-analysis

BACKGROUND: The superior mesenteric artery (SMA) first approach was proposed recently as a new modification of the standard pancreaticoduodenectomy. Increasing evidence showed that a periadventiceal dissection of the SMA with early transection of the inflow during pancreaticoduodenec-tomy associates better early perioperative results, and setup the scene for long-term oncological benefits. The objectives of the current study are to compare the operative results and long-term oncological outcomes of SMA first approach pan-creaticoduodenectomy (SMA-PD) with standard pancreatico-duodenectomy (S-PD).DATA SOURCES: Electronic search of the PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Library was performed until July 2015. We considered randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) comparing SMA-PD with S-PD to be eligible if they included patients with periampullary cancers.RESULTS: A total of one RCT and thirteen NRCSs met the in-clusion criteria, involving 640 patients with SMA-PD and 514 patients with S-PD. The SMA-PD was associated with less in-traoperative bleeding, less blood transfusions and higher rate of associated venous resections. The pancreatic fistula and delayed gastric emptying had a significantly lower rate in the SMA-PD group. There were no differences between the two approaches regarding overall complications, major complica-tion rates and in-hospital mortality. There was no difference regarding R0 resection rate, and one-, two- or three-year over-all survival. The SMA-PD was associated with a lower local, hepatic and extrahepatic metastatic rate.CONCLUSIONS: The SMA-PD is associated with better perioperative outcomes, such as blood loss, transfusion re-quirements, pancreatic fistula, and delayed gastric emptying. Although the one-, two- or three-year overall survival rate is not superior, the SMA-PD has a lower local and metastatic re-currence rate.     

Assessment of the involvement of the macrophage migration inhibitory factor–glucocorticoid regulatory dyad in the expression of matrix metalloproteinase‐2 during periodontitis

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and counter‐regulator of endogenous glucocorticoids (GCs). It is implicated in acute and chronic inflammatory diseases. This study investigated the role of the MIF–GC regulatory dyad in the expression and release of matrix metalloproteinase‐2 (MMP‐2) during periodontitis, in vivo and in vitro. In a Mif‐knockout (KO) mouse model of ligature‐induced periodontitis, gingival tissues and blood were collected and analysed for levels of interleukin‐6 (IL‐6), MIF, MMP‐2, and corticosterone. In addition, human gingival fibroblasts (HGFs) were tested for production of IL‐6 and MMP‐2 after stimulation with hydrocortisone (HC), MIF, tumour necrosis factor‐alpha (TNF‐α), or Fusobacterium nucleatum, a pathogen known to elicit immune responses during periodontitis. Wild‐type (WT) mice showed a local and systemic increase of MIF levels during inflammation, which was confirmed by increased local IL‐6 concentrations. Systemic GC levels were reduced in WT and Mif‐KO mice during inflammation, with overall lower concentrations in Mif‐KO mice. In vivo and in vitro, MMP‐2 production was not dependent on MIF or inflammatory stimuli, but was inhibited by HC. Therefore, MIF does not appear to stimulate expression of MMP‐2 in the gingival tissues, whereas GC upregulates MIF and downregulates MMP‐2. Our findings further suggest that MIF may regulate systemic GC levels.     

Parkes-Weber Syndrome and double orifice atrial septal defect as a combined rare cause of severe pulmonary hypertension

The International Journal of Cardiovascular Imaging -     

Role of 5-HT1A and 5-HT3 receptors in serotonergic activation of sensory neurons in relation to itch and pain behavior in the rat

Serotonin (5-hydroxytryptamine, 5-HT) released by platelets, mast cells, and immunocytes is a potent inflammatory mediator which modulates pain and itch sensing in the peripheral nervous system. The serotonergic receptors expressed by primary afferent neurons involved in these sensory functions are not fully identified and appear to be to a large extent species dependent. Moreover, the mechanisms through which 5-HT receptor activation is coupled to changes in neuronal excitability have not been completely revealed. Using a combination of in vitro (calcium and voltage imaging and patch-clamp) and in vivo behavioral methods, we used both male and female Wistar rats to provide evidence for the involvement of two 5-HT receptor subtypes, 5-HT1A and 5-HT3, in mediating the sustained and transient effects, respectively, of 5-HT on rat primary afferent neurons involved in pain and itch processing. In addition, our results are consistent with a model in which sustained serotonergic responses triggered via the 5-HT1A receptor are due to closure of background potassium channels, followed by membrane depolarization and action potentials, during which the activation of voltage-gated calcium channels leads to calcium entry. Our results may provide a better understanding of mammalian serotonergic itch signaling.     

Response to: Human papillomavirus (HPV) vaccine safety concerning POTS,CRPS and related conditions

Clinical Autonomic Research -