Methylation of the INK4A/ARF locus in blood mononuclear cells

In the detection of DNA hypermethylation as a tumor-specific epigenetic change in blood mononuclear cell fraction in patients with lymphoid and hematopoetic disorders, circulating tumor cells originating from the lymph nodes or bone marrow can be identified. However, it is still not clear whether methylation in mononuclear cells is disease specific. In the present study, we investigated whether methylation of the inhibitor of cyclin-dependent kinase (INK) 4A/alternative reading frame (ARF) locus is present in a disease-specific manner in the blood mononuclear cell fraction of patients with lymphoma, multiple myeloma, or leukemia. To increase the sensitivity of detection, a two-step methylation-specific PCR approach was used to analyze the methylation status of the promoter/exon 1 regions of both p14ARF and p16INK4A genes. Our findings indicate that although INK4A/ARF locus methylation is present in mononuclear cells, this event is not disease-specific since normal subjects also display methylated DNA in their mononuclear cells. In 85.1% of the patients and in 89% of the controls, p16INK4A gene was methylated, while the methylation rates for the p14ARF gene was 32.6 and 36.5%, respectively. The presence of methylated CpG sites in DNA in samples from normal subjects was confirmed by bisulfite genomic sequencing. The difference in the methylation rate between p16INK4A and p14ARF genes among the patients was highly significant (p<0.001). Our results demonstrate that methylation of the INK4A/ARF locus is not a disease-specific molecular change in mononuclear cell fraction and that the p14ARF and p16INK4A genes are differentially methylated.     

The Cost and Consequences of Failed Osteosynthesis of Intertrochanteric Femur Fractures: A Matched Cohort Study

BackgroundWe aimed to evaluate the cost and consequences of failed osteosynthesis of intertrochanteric femur fracture (ITFF) patients and compare with primary ITFF patients.MethodsWe retrospectively evaluated 689 patients who underwent surgery due to ITFF via cephalomedullary nail. 31 patients (5.8%) had revision surgery because of osteosynthesis failure of ITFF. Each revision case included in the study was matched with four primary ITFF cases as control group based on age, gender, year of operation, type of fracture and American Society of Anesthesiologists (ASA) grade. Total cost for the admission that patients underwent surgery, mortality rate at first year, infection rate, length of stay at hospital, length of stay at intensive care unit, and erythrocyte transfusion amounts were recorded from hospital registry records. Tip apex distances (TAD) were noted.ResultsThe mean total cost of the revision cases and primary cases was 10,027 ± 6387 and 5261 ± 1773 Turkish Liras, respectively (p < 0.001). TAD was ≥ 20 mm in 32.3% (10/31) of patients in revision group while 2.4% (3/124) of the patients in control group (p < 0.001). The mean length of stay at hospital, length of stay at intensive care unit, erythrocyte transfusion amounts, infection rate and mortality rate at first year were significantly higher in revision cases compared to matched primary control cases (p < 0.05).ConclusionRevision surgeries due to failed osteosynthesis of ITFFs with cephalomedullary nail have at least two times higher mean total cost than primary cases. The awareness of the cost, morbidity and mortality of the revision surgeries may reduce the modifiable risk factors of osteosynthesis failure including maintenance of TAD below 20 mm, obtaining optimal lag screw position and reduction quality.Level of EvidenceLevel 3, retrospective cohort study.     

Calcaneal osteomyelitis due to Achromobacter xylosoxidans: a case report

Achromobacter xylosoxidans (A. xylosoxidans) has been described as an opportunistic pathogen causing infection. The case we describe is that of an elderly man who had osteomyelitis of calcaneal bone caused by A. xylosoxidans. As far as we are aware there are only 5 cases of osteomyelitis with A. xylosoxidans in the literature. Impaired defensive mechanism of the foot in direct contact with this waterborne bacterium can cause this disease. Because of the high level of antibiotic resistance of this bacterium, clinically more attention should be paid to patients who have impaired defensive mechanisms in their extremities, for example free flaps.     

Anterior palatoplasty for selected mild and moderate obstructive sleep apnea: preliminary results

The aim of this prospective study was to evaluate the long-term efficacy anterior palatoplasty (AP) technique in treatment of patients with mild to moderate obstructive sleep apnea (OSA). Forty-two patients were diagnosed with mild to moderate OSA. Participants were treated with AP for mild or moderate OSA. Patients were evaluated with one night polysomnography before the surgery and 24 months after the surgery. Patients completed Epworth sleepiness scale (ESS), snoring VAS (visual analog scale) before and 24 months after the surgery. Forty two patients with a mean age of 39.2 ± 7.6 were included study. Success rate was 57.1 %. Total apnea-hypopnea index (AHI) values significantly decreased after 2 years (p < 0.025). Non-REM AHI and supine AHI values significantly decreased after 2 years (p < 0.025). The oxygen desaturation index changes significantly decreased after AP (p < 0.025). Snoring VAS values significantly decreased after AP (p < 0.025). ESS scores of patients significantly decreased (p < 0.001). We believe that AP is an effective, inexpensive technique for mild and moderate OSA patients.     

Hypercalcemia Due to Subcutaneous Fat Necrosis in a Newborn After Total Body Cooling

Abstract: Subcutaneous fat necrosis is an inflammatory disorder of adipose tissue. Although patients need long‐term follow‐up to prevent hypercalcemia, the prognosis is generally favorable. We herein present a case of a newborn who developed subcutaneous fat necrosis–related hypercalcemia after hypothermia treatment for hypoxic ischemic encephalopathy. Widespread use of hypothermia treatment for hypoxic ischemic encephalopathy in the neonatal intensive care unit may increase the risk of developing subcutaneous fat necrosis and subsequently hypercalcemia. Great care should be taken to recognize skin findings early in newborns receiving hypothermia treatment, and those diagnosed with subcutaneous fat necrosis require close follow‐up because they are at risk for developing hypercalcemia.     

Stressing the importance of choice: Validity of a preclinical free‐choice high‐caloric diet paradigm to model behavioural,physiological and molecular adaptations during human diet‐induced obesity and metabolic dysfunction

Humans have engineered a dietary environment that has driven the global prevalence of obesity and several other chronic metabolic diseases to pandemic levels. To prevent or treat obesity and associated comorbidities, it is crucial that we understand how our dietary environment, especially in combination with a sedentary lifestyle and/or daily‐life stress, can dysregulate energy balance and promote the development of an obese state. Substantial mechanistic insight into the maladaptive adaptations underlying caloric overconsumption and excessive weight gain has been gained by analysing brains from rodents that were eating prefabricated nutritionally‐complete pellets of high‐fat diet (HFD). Although long‐term consumption of HFDs induces chronic metabolic diseases, including obesity, they do not model several important characteristics of the modern‐day human diet. For example, prefabricated HFDs ignore the (effects of) caloric consumption from a fluid source, do not appear to model the complex interplay in humans between stress and preference for palatable foods, and, importantly, lack any aspect of choice. Therefore, our laboratory uses an obesogenic free‐choice high‐fat high‐sucrose (fc‐HFHS) diet paradigm that provides rodents with the opportunity to choose from several diet components, varying in palatability, fluidity, texture, form and nutritive content. Here, we review recent advances in our understanding how the fc‐HFHS diet disrupts peripheral metabolic processes and produces adaptations in brain circuitries that govern homeostatic and hedonic components of energy balance. Current insight suggests that the fc‐HFHS diet has good construct and face validity to model human diet‐induced chronic metabolic diseases, including obesity, because it combines the effects of food palatability and energy density with the stimulating effects of variety and choice. We also highlight how behavioural, physiological and molecular adaptations might differ from those induced by prefabricated HFDs that lack an element of choice. Finally, the advantages and disadvantages of using the fc‐HFHS diet for preclinical studies are discussed.