Natural History of Cardiac and Respiratory Involvement,Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D

BackgroundType 2C and 2D limb girdle muscular dystrophies (LGMD) are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D.MethodsWe reviewed the charts of 34 LGMD patients, followed from 2005 to 2015, to obtain echocardiographic, respiratory function and sleep recording data. We considered respiratory events (acute respiratory failure, pulmonary sepsis, atelectasis or pneumothorax), cardiac events (acute heart failure, significant cardiac arrhythmia or conduction block, ischemic stroke) and mortality as outcomes of interest for the present analysis.ResultsA total of 21 patients had type 2C LGMD and 13 patients had type 2D. Median age was 30 years [IQR 24–38]. At baseline, median pulmonary vital capacity (VC) was 31% of predicted value [20–40]. Median maximal inspiratory pressure (MIP) was 31 cmH₂O [IQR 20.25–39.75]. Median maximal expiratory pressure (MEP) was 30 cm H₂O [20–36]. Median left ventricular ejection fraction (LVEF) was 55% [45–64] with 38% of patients with LVEF <50%. Over a median follow-up of 6 years, we observed 38% respiratory events, 14% cardiac events and 20% mortality. Among baseline characteristics, LVEF and left ventricular end diastolic diameter (LVEDD) were associated with mortality, whilst respiratory parameters (VC, MIP, MEP) and the need for home mechanical ventilation (HMV) were associated with respiratory events.ConclusionIn our cohort of severely respiratory impaired type 2C and 2D LGMD, respiratory morbidity was high. Cardiac dysfunction was frequent in particular in LGMD 2C and had an impact on long-term mortality.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02501083","term_id":"NCT02501083"}}NCT02501083     

The chemical identification of root promoters extracted from avocado tissues

From the Avocado Rooting Promoter (ARP) 4 compounds were isolated and identified as:

1. 1 acetoxy - 2,4 dihydroxy-n-heptadeca-16-en;
2. 1 acetoxy - 2,4 dihydroxy-n-heptadeca-16-yn;
3. 1,2,4 trihydroxy-n-heptadeca-16-en;
4. 1,2,4 trihydroxy-n-heptadeca-16-yn.

The rooting activity of the pure compounds was verified using the mung bean rooting bioassay. Compound 2II is the most active.     

C-mip interacts with the p85 subunit of PI3 kinase and exerts a dual effect on ERK signaling via the recruitment of Dip1 and DAP kinase

In naive T cells, Lck exerts a negative control on the ERK/MAPK pathway. We show that c-mip (c-maf inducing protein) interacts with the p85 subunit of PI3 kinase and inactivates Lck, which results in Erk1/2 and p38 MAPK activation. This effect is not enough to activate AP1 given the inability of ERK to migrate into the nucleus and to transactivate its target genes. We demonstrate that c-mip interacts with Dip1 and upregulates DAPK, which blocks the nuclear translocation of ERK1/2. This dual effect of c-mip is unique and might represent a potential mechanism to prevent the development of an immune response.

Structured summary

MINT-7383650: p85 (uniprotkb:P27986) physically interacts (MI:0915) with c-Mip (uniprotkb:Q8IY22) by anti bait coimmunoprecipitation (MI:0006)MINT-7383661: c-Mip (uniprotkb:Q8IY22) physically interacts (MI:0915) with p85 (uniprotkb:P27986) by anti tag coimmunoprecipitation (MI:0007)MINT-7383676: p85 (uniprotkb:P27986) physically interacts (MI:0915) with p110 (uniprotkb:P42336) by anti bait coimmunoprecipitation (MI:0006)MINT-7383689, MINT-7383711: Dip-1 (uniprotkb:Q80SY4) physically interacts (MI:0915) with c-Mip (uniprotkb:Q8IY22) by anti tag coimmunoprecipitation (MI:0007)     

Further research at the Oldowan site of Ain Hanech,North-eastern Algeria

Further investigations were carried out at Ain Hanech, Algeria in 1998 and 1999 to explore its potential for investigating early hominid behavioral patterns and adaptation. Research concentrated on the stratigraphy and dating, identifying new archaeological deposits, and excavating the Ain Hanech and El-Kherba localities. To enhance the chronological control within a biostratigraphic framework, the Ain Boucherit fossil-bearing stratum, yielding a Plio-Pleistocene fauna, is correlated with the regional stratigraphy. In the stratigraphic sequence, the Ain Boucherit stratum, located 13m below the Ain Hanech Oldowan occurrences, is found in Unit Q of the Ain Hanech Formation. Unit Q shows a paleomagnetically reversed polarity, which may be correlated with an age earlier than the Olduvai normal subchron (1.95-1.77Ma). Based on test trenches and stratigraphic analyses, additional Oldowan deposits A, B, and C are identified at Ain Hanech. All three deposits and the El-Kherba site contain Mode I technology artefacts associated with an Early Pleistocene fauna. El-Kherba is stratigraphically equivalent to Ain Hanech. These two archaeological sites are estimated to be dated to about 1.8Ma.     

Un nouveau Bovini dans la faune du Pléistocène supérieur d’Algérie

During the study of the Quaternary Maghrebian bovines in 1985, the review of the Bovini (aurochs and buffalos) found in Upper Pleistocene sites of Algeria showed that in comparison with most of the African bovine assemblage the attribution of genus Pelorovis to the species antiquus was inappropriate. The biometric and cladistic data revealed a close kinship with genus Syncerus. Later, other authors’conclusions confirmed its relevance. The antique buffalo of the Aterian site of the Phacochoeri has all the characteristics of genus Syncerus, but is different in that it shows a certain number of specific characteristics described in this article.     

Thirst Perception and Osmoregulation of Vasopressin Secretion Are Altered During Recovery From Septic Shock

Objective

Vasopressin (AVP) secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock.

Design

Prospective interventional study

Setting

Intensive care unit (ICU) at Raymond Poincaré and Etampes Hospitals.

Patients

Normonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock.

Intervention

Osmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 minutes.

Measurements and main results

Plasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60%) were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted.

Conclusion

More than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated.