Proximate causes and consequences of intergenerational influences of salient sensory experience.

Salient sensory environments experienced by a parental generation can exert intergenerational influences on offspring. While these data provide an exciting new perspective on biological inheritance, questions remain about causes and consequences of intergenerational influences of salient sensory experience. We previously showed that exposing male mice to a salient olfactory experience, like olfactory fear conditioning, resulted in offspring demonstrating a sensitivity to the odor used to condition the paternal generation and possessing enhanced neuroanatomical representation for that odor. In this study, we first injected RNA extracted from sperm of male mice that underwent olfactory fear conditioning into naïve single-cell zygotes and found that adults that developed from these embryos had increased sensitivity and enhanced neuroanatomical representation for the odor (Odor A) with which the paternal male had been conditioned. Next, we found that female, but not male offspring sired by males conditioned with Odor A show enhanced consolidation of a weak single-trial Odor A + shock fear conditioning protocol. Our data provide evidence that RNA found in the paternal germline after exposure to salient sensory experiences can contribute to intergenerational influences of such experiences, and that such intergenerational influences confer an element of adaptation to the offspring. In so doing, our study of intergenerational influences of parental sensory experience adds to existing literature on intergenerational influences of parental exposures to stress and dietary manipulations and suggests that some causes (sperm RNA) and consequences (behavioral flexibility) of intergenerational influences of parental experiences may be conserved across a variety of parental experiences.

Reversing Behavioral, Neuroanatomical, and Germline Influences of Intergenerational Stress.

BACKGROUND: Stressors affect populations exposed to them as well as offspring. Strategies preventing the intergenerational propagation of effects of stress would benefit public health. Olfactory cue-based fear conditioning provides a framework to address this issue. METHODS: We 1) exposed adult male mice to an odor, acetophenone (Ace) or Lyral (parental generation [F0]-Exposed), 2) trained mice to associate these odors with mild foot shocks (F0-Trained), and 3) trained mice to associate these odors with mild foot shocks and then extinguished their fear toward these odors with odor-only presentations (F0-Extinguished). We then examined sensitivity of future generation (F1) offspring to these odors, expression of M71 odorant (Ace-responsive) and MOR23 odorant (Lyral-responsive) receptor-expressing cell populations in F1 offspring, and DNA methylation at genes encoding the Ace- (Olfr151, Olfr160) and Lyral- (Olfr16) responsive receptors in F0 sperm. RESULTS: Extinguishing fear toward Ace or Lyral of F0 male mice (F0-Extinguished) that had been fear conditioned with Ace or Lyral, respectively, results in F1-Extinguished offspring that do not demonstrate behavioral sensitivity to Ace or Lyral, respectively, and do not have enhanced representation for M71 or MOR23 odorant receptors in the olfactory system, as is observed in F1-Trained-Ace or F1-Trained-Lyral cohorts, respectively. The promoters of genes encoding Olfr151 and Olfr160 receptors are less methylated in F0-Trained-Ace sperm compared with F0-Exposed-Ace sperm. The Olfr16 promoter is less methylated in F0-Trained-Lyral sperm compared with F0-Exposed-Lyral sperm, and F0-Extinguished-Lyral sperm have methylation levels comparable to F0-Exposed-Lyral sperm. CONCLUSIONS: Our study demonstrates the potential of using extinction-based behavioral strategies to reverse influences of parental stress in offspring and in the parental germline.

Disseminated histoplasmosis diagnosed in the bone marrow of an HIV-infected patient: First case imported in Tunisia.

Histoplasmosis is a fungal infection caused by a dimorphic fungus, Histoplasma capsulatum. We report a first case of disseminated histoplasmosis in a 34-year-old woman, infected with human immunodeficiency virus (HIV), originating from Ivory Coast and living in Tunisia for 4 years. She was complaining from fever, chronic diarrhoea and pancytopenia. The Histoplasma capsulatum var. capsulatum was identified by direct microscopic examination of the bone marrow. She was treated by Amphotericin B, relayed by itraconazole. Even though a regression of symptoms and normalization of blood cell count (BCC), the patient died in a respiratory distress related to CMV hypoxemic pneumonia.

Perineuronal Nets in the Adult Sensory Cortex Are Necessary for Fear Learning.

Lattice-like structures known as perineuronal nets (PNNs) are key components of the extracellular matrix (ECM). Once fully crystallized by adulthood, they are largely stable throughout life. Contrary to previous reports that PNNs inhibit processes involving plasticity, here we report that the dynamic regulation of PNN expression in the adult auditory cortex is vital for fear learning and consolidation in response to pure tones. Specifically, after first confirming the necessity of auditory cortical activity for fear learning and consolidation, we observed that mRNA levels of key proteoglycan components of PNNs were enhanced 4 hr after fear conditioning but were no longer different from the control groups 24 hr later. A similar pattern of regulation was observed in numbers of cells surrounded by PNNs and area occupied by them in the auditory cortex. Finally, the removal of auditory cortex PNNs resulted in a deficit in fear learning and consolidation.

[Predictive value of vitamin D plasma levels on pregnancy rates in a cohort of IVF patients]. / Valeur prédictive du dosage de vitamine D sur les taux de grossesse dans une cohorte de patientes suivies en FIV.

OBJECTIVE: To determine a possible correlation between plasma levels of vitamin D and pregnancy rates obtained by in vitro fertilization (IVF). PATIENTS AND METHODS: One hundred and ninety-eight womens participated in an IVF cycle from January to May 2012 in a prospective study. During the follicular phase locking, serum fluid was collected for vitamin D, calcium, FSH and estradiol analysis. The serum bhCG was checked 16 days after oocyte collect. Clinical pregnancy was confirmed by transvaginal sonography with at least one gestational sac in the uterine cavity. RESULTS: The mean levels of vitamin D was 31.7 nmol/L. A total of 169 patients (85.3%) had a vitamin D insufficiency (< 50 nmol/L). Only 29 patients (14.7%) had a sufficient vitamin D status (vitamin D 50 nmol/L). Pregnancy rate was 29.8% (59/198). There was no significant correlation between the levels of vitamin D and mean age (P = 0.92), BMI (P = 0.16) and etiology of infertility (P = 0.78). In contrast, the levels of vitamin D mean were significantly lower in patients from North Africa (P < 0.0001) and Black African (P = 0.0003) compared to Caucasian patients. DISCUSSION AND CONCLUSION: No correlation was found between serum vitamin D level and the pregnancy rate in IVF cycle.

[Administering GnRH Agonists in the luteal phase of Artificial Cycle Frozen-Thawed Embryo Transfers. A prospective randomized study]. / Administration d'agonistes de la GnRH (Gonadotrophin Releasing Hormone) en phase lutéale des protocoles substitutifs de transferts d'embryons congelés: étude prospective randomisée.

OBJECTIVE: Adding GnRH agonists in the luteal phase has recently been said to improve implantation in IVF treatment (increased rates of pregnancy and birth). Adding GnRH agonists could also be beneficial for frozen-thawed embryo transfers. The objective was to compare the administration of Gonadotropin Releasing Hormone (GnRH) agonists during implantation with usual progesterone supplementation in the artificial cycle of frozen-thawed embryo transfers. METHODS: A prospective randomized controlled trial was conducted in a reproductive medicine center in a university hospital including all women starting an artificial cycle of Frozen-Thawed Embryo Transfers (FET). Two hundred and twenty women were randomized from September 2013 to June 2014. In the addition of GnRh agonists' group, two triptorelin injections of 0.1mg were carried out on the 4th day and on the 6th day following the introduction of progesterone. The primary outcome was the ongoing pregnancy rate. RESULTS: The ongoing pregnancy rate was higher (17 % versus 10.6 % P=0.29) when triptorelin was added, although the difference wasn't significant for the population as a whole. The increase proved to be significant in the case of day 2 embryos (34.6 % versus 10.3 % P<0.05) and of vitrified blastocysts (33.3% versus 12.5% P<0.05). CONCLUSION: The ongoing pregnancy rate for day 2 embryos and vitrified blastocysts significantly increased when GnRH agonists were added during implantation.

Acute efficacy of a sublingual dose of nifedipine on uterine arterial blood flow: preliminary data in prematurely menopausal women.

OBJECTIVES: To determine whether the calcium blocker nifedipine alters Doppler velocimetry and impedance parameters in the uterine artery in prematurely menopausal women. METHODS: Uterine artery Doppler examinations were performed transvaginally in seventeen prematurely menopausal women without the use of calcium blocker (T0). Following a 10-mg sublingual dose of nifedipine patients were subsequently rescanned at successive time intervals (T25 = 25, T40 = 40, T60 = 60 min). PI (normalized (NPI) for heart rate) and maximum, minimum and average velocities of the uterine artery were recorded and waveforms were qualitatively assessed using Goswamy and Steptoe's waveform classification. RESULTS: Quantitative analysis showed a significant decrease in NPI at T(25) in the right and left uterine arteries (T0: PI = 2.95 and 3.01; T25: PI = 1.52 and 1.52, respectively; P < 0.001) and until the end of the experiment. Minimum and average blood flow velocities increased strongly (P < 0.001) whereas the maximum velocities did not change significantly (P = 0.12). Qualitative analysis revealed more conspicuous results: eight subjects presented 'abnormal' spectra: one was type A (absence of protodiastole), three were type B (absence of telediastole) and four were type O (no diastolic blood flow); all of them recovered type C waveforms (normal spectrum) during the hour following nifedipine administration. CONCLUSIONS: Nifedipine induces a reversible decrease in NPI and an increase in blood flow velocities in the uterine artery in prematurely menopausal women. These results suggest that nifedipine is a potent uterine arterial vasodilator.

[Primary hypertrophic osteoarthropathy without cutaneous involvement (Currarino's disease)]. / Ostéoarthropathie hypertrophiante primitive sans atteinte cutanée (maladie de Currarino).

INTRODUCTION: Hypertrophic osteoarthropathy (HOA) is a syndrome associating hippocratic fingers, arthropathy and periostosis of long bones. Currarino's disease, considered at present as a clinical form of primary HOA, is characterized by the absence of pachydermia. OBSERVATION: A 24-year-old Caucasian man, consulted for a painful swelling of both ankles that had developed over the past year. Clinical examination revealed hippocratic fingers without pachydermia. The ankles were swollen. The X-rays showed periosteal apposition and an acro-osteolysis. In view of this triad: arthropathy, hippocratic fingers and periostosis, primary HOA without cutaneous involvement or Currarino's disease was diagnosed. The search for a secondary cause remained negative. Clinical improvement was obtained after 15 months with non-steroidal anti-inflammatory drugs (NSAID) and colchicine. COMMENTS: Although exceptional, primary HOA without cutaneous involvement is a genetic disease which must not be ignored.

Comparison of two blastocyst culture systems: coculture on Vero cells and sequential media.

OBJECTIVE: To compare two blastocyst culture systems: culture on Vero cells and sequential media in the same time period. DESIGN: Retrospective study. SETTING: Institutional practice assisted reproductive technology center. PATIENT(S): Ninety-nine selected patients undergoing IVF with blastocyst culture. INTERVENTION(S): In vitro fertilization and transfer of at least one expanded blastocyst after culture using either Vero cells or sequential media (S(2) medium). MAIN OUTCOME MEASURE(S): Blastocyst, pregnancy, and implantation rates. RESULT(S): The blastocyst formation rate (41.6% vs. 31.6%) is significantly increased with sequential media compared with the coculture system, but there is no statistically significant difference in the pregnancy and implantation rates (39.5% vs. 38.6% and 23.7% vs. 15.1%, respectively). CONCLUSION(S): Blastocyst culture on sequential media offers a better dynamic of embryo development (22% vs. 13.6% blastocyst at day 5). There was no statistically significant difference between the two groups in the take-home baby rate (18 vs. 12).

[A simple technic for vaginal suspension using multiple approaches. Study of a series of 50 cases]. / Une technique simple de colposuspension par voie mixte. Etude d'une série de 50 cas.

Fifty patients underwent vaginal suspension using a new technique based on Stamey's procedure. The method of operation is described with illustrations. This procedure can be carried out with the patient in the lithotomy position when special indications are present: when prolapse has to be cured by the vaginal route and a vaginal suspension has to be carried out; when a vaginal hysterectomy has to be carried out together with a vaginal suspension; when an upper approach vaginal suspension using a Marshall-Marchetti technique has failed. The advantages of this technique seem to the authors to be: the simplicity of the procedure: only the lithotomy position is needed. It is easy and quick to carry out, it is safe: dissecting out the bladder from the vaginal approach and passing threads from below to above practically completely avoids the risk of damaging the bladder. The preliminary clinical and uro-dynamic results are given.

Renal magnesium and phosphate wastage in a patient with hypercalciuria and nephrocalcinosis: effect of oral phosphorus and magnesium supplements.

We report a 29-year-old man with a mild decrease in glomerular filtration, nephrocalcinosis, hypercalciuria and a renal magnesium leak. He had other features of 'congenital magnesium-losing kidney', such as arthritis and hyperuricemia, short stature and recurrent urinary tract infections, but had no radiological chondrocalcinosis. In addition, pallidal calcification was found. The patient also had a renal phosphate leak. Phosphorus supplements resulted in a decrease in urinary calcium excretion, indicating that hypercalciuria was at least partially a consequence of phosphorus depletion. Plasma and urine magnesium were not affected by phosphorus supplements. Addition of magnesium supplements resulted in a transient and modest decrease in urinary calcium excretion, with no modification in plasma magnesium.