The role of macrophages and dendritic cells in the clearance of apoptotic cells in advanced atherosclerosis

Accumulating evidence supports the notion that defective phagocytic clearance of dying cells, or defective "efferocytosis," is causally linked to the progression of advanced atherosclerosis. In advanced atherosclerotic lesions, defective efferocytosis leads to post-apoptotic necrosis, expansion of plaque necrotic cores, and susceptibility to atherothrombosis. Both macrophages and DC-like efferocytes are juxtaposed near expanding necrotic cores, where they engage apoptotic cells. In this Viewpoint, we discuss how reduced efferocytosis by macrophages and CD11c(HI) DC-like cells may combine to reduce overall plaque stability and therefore promote susceptibility to acute atherothrombosis.     

Neurons in the human hippocampus and amygdala respond to both low- and high-level image properties

A large number of studies have demonstrated that structures within the medial temporal lobe, such as the hippocampus, are intimately involved in declarative memory for objects and people. Although these items are abstractions of the visual scene, specific visual details can change the speed and accuracy of their recall. By recording from 415 neurons in the hippocampus and amygdala of human epilepsy patients as they viewed images drawn from 10 image categories, we showed that the firing rates of 8% of these neurons encode image illuminance and contrast, low-level properties not directly pertinent to task performance, whereas in 7% of the neurons, firing rates encode the category of the item depicted in the image, a high-level property pertinent to the task. This simultaneous representation of high- and low-level image properties within the same brain areas may serve to bind separate aspects of visual objects into a coherent percept and allow episodic details of objects to influence mnemonic performance.     

Treatment of older adults with co-morbid personality disorder and depression: a dialectical behavior therapy approach

BACKGROUND AND SIGNIFICANCE: The treatment of personality disorders in older adults, particularly those co-morbid with other Axis I disorders (e.g., Major Depressive Disorder), is an understudied clinical phenomenon. It has also been demonstrated that personality disorders in older adults complicate treatment of other psychopathology, as well as result in heightened interpersonal disturbance and emotional distress. METHODS: Two studies utilizing standard Dialectical Behavior Therapy (DBT) to treat depression and personality disorders in older adults are reviewed. Study 1 examined 34 chronically depressed individuals aged 60 and older who were randomly assigned to receive 28 weeks of antidepressant medication plus clinical management, either alone (MED) or with the addition of DBT skills-training and scheduled telephone coaching sessions (MED + DBT). Study 2 had two phases of treatment: Phase I: 8-week open-trial of antidepressant medication (n = 65); Phase II: 24-week randomized trial of DBT + MED versus MED alone for those who prospectively failed to respond to the Phase I medication trial (n = 37). RESULTS: Study 1 demonstrated that 71% of MED + DBT patients were in remission at post-treatment, in contrast to 47% of MED patients. This became a significant difference at the 6-month follow-up; where 75% of MED + DBT-D patients were in remission compared with only 31% of MED patients. Study 2 showed that after 8 weeks of treatment with antidepressant medication alone (Phase 1) only 14% of the sample had at least a 50% reduction in HAM-D scores. Phase II results showed on average, the DBT + MED group reached depression remission by the post-group assessment and maintained these gains while the MED group did not reach remission, until the follow-up assessment. Results demonstrated superiority of DBT + MED compared to MED alone on Interpersonal Sensitivity and Interpersonal Aggression at post-treatment and 6-month follow-up. CONCLUSION: Results from these two treatment development studies indicate that applying standard DBT for the treatment of co-morbid MDD or MDD + PD in older adults is feasible, acceptable, and has clinical promise. Modifications to standard DBT and an overview of a new treatment manual for this population are summarized.     

Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

Pregnancy from intracytoplasmic sperm injection of a sperm head and detached tail

OBJECTIVE: To evaluate sperm ultrastructure and the efficacy of intracytoplasmic sperm injection (ICSI) with careful positioning of the sperm midpiece next to the sperm head in a patient with easily decapitated sperm syndrome. DESIGN: In vitro fertilization case report with retrospective sperm ultrastructure analysis. SETTING: In vitro fertilization clinic and andrology laboratory. PATIENT(S): A couple seeking treatment for diminished ovarian reserve and male factor infertility using donor oocyte IVF. INTERVENTION(S): Motile sperm inadvertently decapitated during micromanipulation were used for a modified ICSI procedure in which the midpiece was carefully positioned proximal to the sperm head. Sperm were also analyzed by transmission electron microscopy (TEM). MAIN OUTCOME MEASURE(S): Fertilization rate, embryo development, pregnancy, and the incidence of normal sperm ultrastructure. RESULT(S): The ICSI resulted in a fertilization rate of 63% and embryo development of good to moderate quality of 36% of the embryos. Transfer of two embryos resulted in a pregnancy and birth of a healthy child. Normal sperm centrosomes were identified retrospectively. CONCLUSION(S): Pregnancy can result in patients where the sperm are decapitated during immobilization before ICSI if normal centrosomes are present and the head and midpiece are positioned closely together.     

Mineral balance and whole body bone mineral content in very low-birth-weight infants

Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants ( 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65±14 and 62±9mg/kg/day versus 55±12 and 47±7mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5±0.4 g/kg/day and 88±4% versus 4.2±1 g/kg/day, 79±6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3±30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6±36.6g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups. The deficit in the 12 subjects who had a BMCt under 30 g at 3 months of age had been corrected at age 6 months. Premature babies fed a pooled pasteurized human milk enriched with calcium, phosphorus and magnesium favored a better retention of calcium and phosphorus. However, no significant influence of the two diets studied was observed on the gain in BMCt over the first 6 months of life.     

Relationship between pain and medial knee joint loading in mild radiographic knee osteoarthritis

OBJECTIVE: The relationship between knee pain and radiographic evidence of knee osteoarthritis (OA) is notoriously imperfect. In particular, conditions that distinguish individuals with symptoms from those with comparable radiographic involvement who remain asymptomatic are unclear. We investigated dynamic loading across the knee in individuals with mild radiographic OA who were distinguished by the presence or absence of knee pain. METHODS: Subjects were recruited into 3 groups: symptomatic with a Kellgren/Lawrence (K/L) grade of 2 (n = 52), asymptomatic with a K/L grade of 2 (n = 19), and asymptomatic with a K/L grade of 0 or 1 (n = 37), the latter representing a normal comparator group. Dynamic knee loading was assessed with gait analysis, and both the peak external knee adduction moment and the knee adduction angular impulse were determined. RESULTS: Peak knee adduction moment and knee adduction angular impulse were 19% and 30% higher, respectively, in symptomatic K/L grade 2 individuals than in asymptomatic individuals with the same radiographic grade (P < 0.05). Conversely, the asymptomatic K/L grade 2 group did not differ from the K/L grade 0-1 normal comparator group (P = 1.00). CONCLUSION: Among individuals with mild radiographic knee OA (K/L grade 2), those who are symptomatic have significantly higher medial compartment loads than those who are asymptomatic, whereas those who are asymptomatic do not differ from normal controls (asymptomatic K/L grade 0 or 1). These findings suggest a biomechanical component to the distinction between asymptomatic and symptomatic radiographic OA, which may be pathophysiologically important.