Résilience familiale et transmission transgénérationnelle du traumatisme de la Shoah

The clinical concepts developed in the present paper concern the resilience and the trans-generational transmission among families of Holocaust survivors. In physical terms, "resilience" is defined as the ability of a material to regain its shape or original position after having been compressed or stretched. In human sciences, “resilience” is the capacity of certain individuals either to adapt successfully to adversity, or to function in a competent manner when faced with a traumatic situation. The concept of trans-generational transmission of trauma is mentioned by numerous authors in explaining certain types of psychological suffering endured by several generations of the same family, notably among descendants of Holocaust survivors. In some traumatized families, all the energy is used by a mourning process and by strategies of survival. Memory of death is everywhere and memory of life is repressed. To help those families, psychotherapists have to inverse the situation by revealing the memory of life and by limiting the role of the memory of death. We present here several clinical observations that we made during therapy sessions with certain families of Holocaust survivors. These families consulted with us because of the symptoms presented by members of the third generation (the grandchildren of the Holocaust survivors) as adolescents. These symptoms were not specific, and included various categories such as dropping out of school, behavior problems, self-mutilation, eating disorders, drug abuse, depressive or anxiety disorders, and problems with aggression. These families presented some specific patterns in their relationships, which led us to consider that the symptoms presented by the third generation might be a consequence of the family's history and the trans-generational transmission of Holocaust trauma. We also describe here the clinical strategy that we developed to assist these families. This strategy was used in addition to classical individual and linear treatment of the symptoms and consisted of an attempt to reinforce the relationships between Holocaust survivors and their grandchildren with the aim of stimulating a structuring trans-generational transmission. In effect, at the liberation of the camps, certain Holocaust survivors used, as a mechanism of individual resilience, control over their memory and their emotions. In effect, their psychological survival was impossible without making sure that their terrible memories and inexpressible feelings could not occupy their consciousness. In stifling their memories and their history, they created a void in the parenting of their children and their grandchildren. In order to fill this void and to unblock familial memory, we make use of the privileged position occupied by the grandchildren of Holocaust survivors. In effect, Holocaust survivors generally adopt a more flexible attitude toward their grandchildren than toward their children. Therefore, we entrusted them with the task of reconstructing the history of their family before and after the Holocaust through consulting their grandparents, most of all, but also other members of the family, whether it be directly or by courier (eventually electronic, in the case of geographic separation). Our therapeutic approach improves the flexibility, adaptability and communication of the family. Moreover, it improves the bond between Holocaust survivors and their grandchildren and permits the latter, through a better knowledge of their family history, to acquire a trans-generational shadow.     

Transmission clustering drives the onward spread of the HIV epidemic among men who have sex with men in Quebec

Phylodynamic analysis and epidemiologic data identified 3 patterns of spread of primary human immunodeficiency virus type 1 infection (PHI) among men who have sex with men (2001-2009): 420 unique PHIs, 102 small clusters (2-4 PHIs per cluster, n = 280), and 46 large clusters (5-31 PHIs per cluster, n = 450). Large clusters disproportionately increased from 25.2% of PHIs in 2005 to 39.1% in 2009 (χ(2) = 33.9, P < .001). Scalar expansion of large clusters over 11 months (interquartile range, 3.5-25.5 months) correlated with cluster membership size (r(2) = 0.174, F = 4.424, P = .047). PHI cohort data revealed variations in social networks and risk behaviors among the 3 groups, suggesting the need for tailored prevention measures.     

Cognitive impairment in fatigue and sleepiness associated conditions

Although relating to very different concepts, sleepiness and fatigue are often confounded. However, both fatigue-associated conditions such as the chronic fatigue syndrome (CFS) and sleepiness-associated conditions such as the sleep apnea-hypopnea syndrome (SAHS) are associated with cognitive impairment with impaired attention, concentration and memory performances. Fifteen pure CFS patients, without primary sleep disorders or clinically relevant sleepiness, were compared to 15 untreated SAHS patients, without clinically relevant fatigue, and to 16 healthy controls of similar age. The auditory verbal learning test (AVLT), digit span, digit symbol and finger tapping test (FTT) were used as cognitive and behavioural measures. In addition we assessed daytime EEG spectral power and P300 evoked potentials. With exception for the digit span, all tests showed lower performances in patient groups. Recall on the AVLT did not differ between the two patient groups, but the digit and symbol spans showed more severe impairment in SAHS patients. Psychomotor performance on the FTT presented with slower hit rates in SAHS than in CFS. EEG theta power was highest in CFS patients. P300 latencies and amplitudes did not differ between groups. Fatigue- and sleepiness-associated conditions can both present with significant and objective impairment of cognitive functioning and behavioural motor performance. In our sample cognitive impairment and psychomotor performance were worse when associated to sleepiness in SAHS than with fatigue in CFS.     

Altered interaction between cardiac vagal influence and delta sleep EEG suggests an altered neuroplasticity in patients suffering from major depressive disorder

Jurysta F, Kempenaers C, Lancini J, Lanquart J‐P, van de Borne P, Linkowski P. Altered interaction between cardiac vagal influence and delta sleep EEG suggests an altered neuroplasticity in patients suffering from major depressive disorder. Objective: Major depressive disorder (MDD), which is associated with altered neuroplasticity and increased relative cardiac sympathic activity, enhances the risk of cardiovascular pathologies. Interaction between cardiac sympatho‐vagal indexes and delta sleep power is probably altered in MDD. Method: Sleep characteristics and cardiac sympatho‐vagal indexes of 10 depressive patients were compared to 10 control men across the first three non‐rapid eye movement (NREM)–REM cycles. Interaction between normalized high frequency (HF) and delta power bands was studied using coherence analysis. Results: Patients showed increased sleep latency, stage 1 and wake durations. No differences in heart rate variabilities were observed: Total power, HF and RR‐interval decreased from NREM to REM sleep and wakefulness in both groups. Gain value was lower in patients while coherence and phase shift were similar between groups. Modifications in HF appear 8 min before modifications in delta. Conclusion: Major depressive disorder is related to an altered link between cardiac vagal influence and delta sleep, suggesting disorders in cardiovascular controls and an altered neuroplasticity.     

99mTc]HYNIC-RGD for imaging integrin alphavbeta3 expression

There has been increasing interest in peptides containing the Arg-Gly-Asp (RGD) sequence for targeting of alpha(v)beta(3) integrins to image angiogenesis. [(18)F]Galacto-RGD has been successfully used for positron emission tomography applications in patients. Here we report on the preclinical characterization of a (99m)Tc-labeled derivative for single-photon emission computed tomography. c(RGDyK) was derivatized with HYNIC at the amino group of the lysine [c(RGDyK(HYNIC)) or HYNIC-RGD]. (99m)Tc labeling was performed using coligands (tricine and EDDA), as well as (99m)Tc(CO)(3)(H(2)O)(3). Radiolabeled peptides were characterized with regard to lipophilicity, protein binding and stability in buffer, serum and tissue homogenates. Integrin receptor activity was determined in internalization assays using alpha(v)beta(3)-receptor-positive M21 and alpha(v)beta(3)-receptor-negative M21L melanoma cells. Biodistribution was evaluated in normal and nude mice bearing M21, M21L and small cell lung tumors. HYNIC-RGD could be labeled at high specific activities using tricine, tricine-trisodium triphenylphosphine 3,3',3'-trisulfonate (TPPTS), tricine-nicotinic acid (NA) or EDDA as coligands. [(99m)Tc]EDDA/HYNIC-RGD, [(99m)Tc]tricine-TPPTS/HYNIC-RGD and [(99m)Tc]tricine-NA/HYNIC-RGD showed protein binding (<5%) considerably lower than [(99m)Tc](CO)(3)/HYNIC-RGD and [(99m)Tc]tricine/HYNIC-RGD. [(99m)Tc]EDDA/HYNIC-RGD revealed high in vitro stability accompanied by low lipophilicity with a log P value of -3.56, comparable to that of [(18)F]Galacto-RGD. In M21 cells for this compound, the highest level of specific and rapid cell uptake (1.25% mg protein(-1)) was determined. In vivo, rapid renal excretion, low blood retention, low liver and muscle uptakes and low intestinal excretion 4 h postinjection were observed. Tumor uptake values were 2.73% ID/g in M21 alpha(v)beta(3)-receptor-positive tumors versus 0.85% ID/g in receptor-negative tumors 1 h postinjection. Small cell lung tumors could be visualized using gamma camera imaging. [(99m)Tc]EDDA/HYNIC-RGD shows encouraging properties to target alpha(v)beta(3) receptors in vivo with high stability and favorable pharmacokinetics. Tumor uptake studies showed specific targeting of alpha(v)beta(3)-receptor-positive tumors with tumor-to-organ ratios comparable to those of [(18)F]Galacto-RGD.