Advancing maternal and perinatal health in low- and middle-income countries: A multi-country review of policies and programmes.

The Sustainable Development Goals prioritize maternal mortality reduction, with a global average target of < 70 per 100,000 live births by 2030. Current pace of reduction is far short of what is needed to achieve the global target. It is estimated that globally there are 300,000 maternal deaths, 2.4 million newborn deaths and 2 million stillbirths annually. Majority of these deaths occur in low-and-middle-income countries. Global initiatives like, Ending Preventable Maternal Mortality (EPMM) and Every Newborn Action Plan (ENAP), have outlined the broad strategies for maternal and newborn health programmes. A set of coverage targets and ten milestones were launched to support low-and-middle-income countries in accelerating progress in improving maternal, perinatal and newborn health and wellbeing. WHO, UNICEF and UNFPA, undertook a scoping review to understand how country strategies evolved in different contexts over the past two decades to improve maternal survival and wellbeing, and how countries in similar settings could accelerate progress considering the changing epidemiology and demography. Case studies were conducted to inform countries in similar settings and various global initiatives. Six countries were selected based on standard criteria-Cambodia, Democratic Republic of the Congo, Georgia, Guatemala, Pakistan and Sierra Leone representing different stages of the obstetric transition. A conceptual framework, encapsulating the interrelated factors impacting maternal health outcomes, was used to organize data collection and analysis. While all six countries made remarkable progress in improving maternal and perinatal health, the pace of progress and the factors influencing the successes and challenges varied across the countries. The context, opportunities and challenges varied from country to country. Two strategic directions were identified for next steps including the need to implement and evaluate innovative service delivery models using an updated obstetric transition as an organizing framework and expanding our vision to address equity and well-being.

An epidemiologic retrospective study of maxillofacial traumatology in the elderly.

INTRODUCTION: The elderly population, which is more active than before, is increasingly suffering from trauma (loss of reflexes and systemic pathologic conditions). Surgical management may be more controversial due to the potential consequences of general anesthesia and the sometimes negligible consequences of functional management. The main objective of this study was to analyze the causes and location of facial fractures in subjects older than 65 years. The secondary objective was to evaluate the management of these fractures (surgical or functional) according to comorbidities. MATERIAL & METHODS: In this retrospective study (over a five-year period), we analyzed the causes and management of facial fractures in patients aged over 65 years, and the medical history of each patient was investigated. RESULTS: One hundred and nineteen patients with 198 facial fractures were included. The main cause of fractures was a fall (50%). The zygomatic region (39.9%) and mandible (27.8%) were the sites of the most frequent fractures. Comorbidities were found in 84.9% of patients, the majority of which were cardiovascular diseases (82.3%). 75.8% of fractures were treated surgically and 4.8% of patients had complications. DISCUSSION: This work is a help to understanding the causes and consequences of facial trauma in the elderly population. The management of these facial fractures requires a multidisciplinary assessment, taking into account the patient's medical history and evaluating the risks and benefits of a surgical procedure with general anesthesia.

Intraoperative cone beam assessment after reduction of zygomatic fractures helps in taking a decision on associated orbital floor fractures.

INTRODUCTION: Orbital floor fracture (OFF) are frequently associated with zygomatic fractures (ZF). The reduction of the ZF may modify the features of the associated OFF. Intraoperative cone beam CT (CBCT) has shown diagnostic performance of OFF. The aim of our study was to evaluate how intraoperative CBCT control made after the reduction of ZF may help to take a decision on the associated OFF. MATERIAL AND METHOD: Patients with a unilateral displaced ZF associated with an OFF were consecutively included during a 3-year period. Intraoperative CBCT, systematically performed after reduction of the ZF, allowed to decide if the OFF needed reconstruction. The preoperative estimation made on MDCT and the intraoperative decision regarding the OFF were compared. RESULTS: Fifty-nine consecutive patients could be included in the study. Nineteen OFF were presumed to be surgical indications on the preoperative MDCT but only 16 indications were confirmed on the intraoperative CBCT, meaning that 3 OFF behaved favorably during the ZF reduction. Forty orbital floor fractures were presumed to be non-surgical on the preoperative MDCT but 6 of them worsened during ZF reduction and became surgical indications. Overall, the intraoperative CBCT control had an impact on 9 (15.3%) of the OFF. CONCLUSION: Our study showed that OFF after ZF reduction may evolve favorably or, on the contrary, get worse in 15% of the cases. Surgical indication on an OFF can therefore be confirmed intraoperatively. This allows to avoid under-treatment in the patients where the OFF worsens after ZF reduction and over-treatment in the patient where the OFF reduces after ZF.

Detection of Cross-Correlation between Gravitational Lensing and γ Rays.

In recent years, many γ-ray sources have been identified, yet the unresolved component hosts valuable information on the faintest emission. In order to extract it, a cross-correlation with gravitational tracers of matter in the Universe has been shown to be a promising tool. We report here the first identification of a cross-correlation signal between γ rays and the distribution of mass in the Universe probed by weak gravitational lensing. We use data from the Dark Energy Survey Y1 weak lensing data and the Fermi Large Area Telescope 9-yr γ-ray data, obtaining a signal-to-noise ratio of 5.3. The signal is mostly localized at small angular scales and high γ-ray energies, with a hint of correlation at extended separation. Blazar emission is likely the origin of the small-scale effect. We investigate implications of the large-scale component in terms of astrophysical sources and particle dark matter emission.

Cosmological Constraints from Multiple Probes in the Dark Energy Survey.

The combination of multiple observational probes has long been advocated as a powerful technique to constrain cosmological parameters, in particular dark energy. The Dark Energy Survey has measured 207 spectroscopically confirmed type Ia supernova light curves, the baryon acoustic oscillation feature, weak gravitational lensing, and galaxy clustering. Here we present combined results from these probes, deriving constraints on the equation of state, w, of dark energy and its energy density in the Universe. Independently of other experiments, such as those that measure the cosmic microwave background, the probes from this single photometric survey rule out a Universe with no dark energy, finding w=-0.80_{-0.11}^{+0.09}. The geometry is shown to be consistent with a spatially flat Universe, and we obtain a constraint on the baryon density of Ω_{b}=0.069_{-0.012}^{+0.009} that is independent of early Universe measurements. These results demonstrate the potential power of large multiprobe photometric surveys and pave the way for order of magnitude advances in our constraints on properties of dark energy and cosmology over the next decade.

Self-Propelled Particles with Velocity Reversals and Ferromagnetic Alignment: Active Matter Class with Second-Order Transition to Quasi-Long-Range Polar Order.

We introduce and study in two dimensions a new class of dry, aligning active matter that exhibits a direct transition to orientational order, without the phase-separation phenomenology usually observed in this context. Characterized by self-propelled particles with velocity reversals and a ferromagnetic alignment of polarities, systems in this class display quasi-long-range polar order with continuously varying scaling exponents, yet a numerical study of the transition leads to conclude that it does not belong to the Berezinskii-Kosterlitz-Thouless universality class but is best described as a standard critical point with an algebraic divergence of correlations. We rationalize these findings by showing that the interplay between order and density changes the role of defects.

First steps to define murine amniotic fluid stem cell microenvironment.

Stem cell niche refers to the microenvironment where stem cells reside in living organisms. Several elements define the niche and regulate stem cell characteristics, such as stromal support cells, gap junctions, soluble factors, extracellular matrix proteins, blood vessels and neural inputs. In the last years, different studies demonstrated the presence of cKit+ cells in human and murine amniotic fluid, which have been defined as amniotic fluid stem (AFS) cells. Firstly, we characterized the murine cKit+ cells present both in the amniotic fluid and in the amnion. Secondly, to analyze the AFS cell microenvironment, we injected murine YFP+ embryonic stem cells (ESC) into the amniotic fluid of E13.5 wild type embryos. Four days after transplantation we found that YFP+ sorted cells maintained the expression of pluripotency markers and that ESC adherent to the amnion were more similar to original ESC in respect to those isolated from the amniotic fluid. Moreover, cytokines evaluation and oxygen concentration analysis revealed in this microenvironment the presence of factors that are considered key regulators in stem cell niches. This is the first indication that AFS cells reside in a microenvironment that possess specific characteristics able to maintain stemness of resident and exogenous stem cells.

Improvement of diaphragmatic performance through orthotopic application of decellularized extracellular matrix patch.

Muscle tissue engineering can provide support to large congenital skeletal muscle defects using scaffolds able to allow cell migration, proliferation and differentiation. Acellular extracellular matrix (ECM) scaffold can generate a positive inflammatory response through the activation of anti-inflammatory T-cell populations and M2 polarized macrophages that together lead to a local pro-regenerative environment. This immunoregulatory effect is maintained when acellular matrices are transplanted in a xenogeneic setting, but it remains unclear whether it can be therapeutic in a model of muscle diseases. We demonstrated here for the first time that orthotopic transplantation of a decellularized diaphragmatic muscle from wild animals promoted tissue functional recovery in an established atrophic mouse model. In particular, ECM supported a local immunoresponse activating a pro-regenerative environment and stimulating host muscle progenitor cell activation and migration. These results indicate that acellular scaffolds may represent a suitable regenerative medicine option for improving performance of diseased muscles.

Reprogramming of mouse amniotic fluid cells using a PiggyBac transposon system.

Induced pluripotent stem (iPS) cells are generated from mouse and human somatic cells by forced expression of defined transcription factors using different methods. Amniotic fluid (AF) cells are easy to obtain from routinely scheduled procedures for prenatal diagnosis and iPS cells have been generated from human AF. Here, we generated iPS cells from mouse AF cells, using a non-viral-based approach constituted by the PiggyBac (PB) transposon system. All iPS cell lines obtained exhibited characteristics of pluripotent cells, including the ability to differentiate toward derivatives of all three germ layers in vitro and in vivo.

Fear of hypoglycaemia in patients with type 1 diabetes: do patients and diabetologists feel the same way?

AIM: This study described and compared the perception of hypoglycaemia in both patients with type 1 diabetes and diabetologists. METHODS: This was an observational cross-sectional study undertaken in France in 2011. Data for what hypoglycaemia represents and practices related to it were collected using a questionnaire completed by patients with type 1 diabetes (all>12 years of age) and their diabetologists. Agreement between patients and physicians was evaluated by the intraclass correlation coefficient (ICC) and Gwet's coefficient (GC). RESULTS: A total of 485 patients were enrolled by 118 diabetologists. Half the patients thought that hypoglycaemia was always symptomatic. According to both patients and diabetologists, hypoglycaemia impaired quality of life, caused anxiety and was disturbing, especially at night. Clinical symptoms of hypoglycaemia (sweating, shakiness, anxiety) were linked to patient's age and diabetes duration. Regarding hypoglycaemia frequency, agreement was good for severe hypoglycaemia (GC: 0.61 and 0.72 for diurnal and nocturnal hypoglycaemia, respectively) and poor for mild hypoglycaemia (ICC: 0.44 and 0.40, respectively). Diabetologists correctly evaluated the impact of hypoglycaemia on quality of life, but overestimated the hypoglycaemia-induced burden and anxiety. Counteractive behaviours were frequent: 23% of patients decreased their insulin dose, 20% increased their sugar intake and 12% ate extra snacks. Diabetologists were generally aware of these measures, but not of how often patients used them. CONCLUSION: Diabetologists and patients do not share enough information about hypoglycaemia. Fear of hypoglycaemia and counteractive behaviours should be looked for by diabetologists. Systematic advice and specially adapted education should also be provided to increase patients' awareness of hypoglycaemia.

The clinical variability of maternally inherited diabetes and deafness is associated with the degree of heteroplasmy in blood leukocytes.

CONTEXT: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. OBJECTIVE: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. PARTICIPANTS: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. RESULTS: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA(1c) was also found and remained significant after adjustment for age at molecular sampling and gender. CONCLUSIONS: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.

Retinal and renal complications in patients with a mutation of mitochondrial DNA at position 3,243 (maternally inherited diabetes and deafness). A case-control study.

AIMS/HYPOTHESIS: We assessed the prevalence and determinants of retinal and renal complications in patients with maternally inherited diabetes and deafness (MIDD). METHODS: This was a multicentre prospective study comparing the prevalence of retinopathy and renal disease in 74 patients with MIDD and 134 control patients matched for sex, age and clinical presentation at onset of diabetes, duration of diabetes and current treatment. Comparisons were adjusted for HbA(1c) and hypertension. RESULTS: In MIDD patients, HbA(1c) (7.6 +/- 1.6 vs 8.5 +/- 2.0%, p < 0.002), systolic blood pressure (126.6 +/- 16.2 vs 133.1 +/- 17.3 mmHg, p < 0.007) and prevalence of hypertension (33.8 vs 64.2%, p < 0.0001) were lower than in control patients. Prevalence of diabetic retinopathy was 3.7-fold lower in MIDD patients (6/74, 8 vs 40/134, 29.6%, p < 0.0001). Differences between groups remained significant after adjustment for hypertension, systolic blood pressure and HbA(1c). In MIDD, urinary albumin excretion (314.8 vs 80.1 mg/24 h, p = 0.035) and creatinine plasma levels (103.5 vs 82.2 micromol/l, p = 0.0178) were higher and GFR was lower. Impaired renal function (GFR <60 ml/min) was four- to sixfold more frequent in MIDD. Differences between MIDD and control diabetic patients further increased when adjusted for HbA(1c) and systolic blood pressure (p < 0.0001). Adjustment for treatment with an ACE inhibitor or angiotensin II receptor antagonist did not modify the results. CONCLUSIONS/INTERPRETATION: This study indicates that diabetic retinopathy is less prevalent in MIDD than in control diabetes. This suggests that retinal alterations due to mitochondrial disease may have a protective role. By contrast, nephropathy is far more frequent in MIDD, suggesting the presence of a specific renal disease independent of diabetic nephropathy.

[Routine medical management of obesity]. / Prise en charge de l'obésité en pratique par le médecin.

Management of obesity is often reduced to counselling, focusing on factors directly affecting energy balance: food intake and physical activity. However, the causes of excessive food intake, eating disorders and their causal factors, are largely unknown. This can lead to unsuitable obesity management. In the present text, we detail the clinical elements which can be helpful for the specialist or general practitioner making a global assessment of their overweight patients. The goal is to help the patient establish a care project with medical support, as would be the case for any chronic disease.

Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD).

OBJECTIVE: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes. OBJECTIVE: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD. DESIGN: Multicenter prospective study. PATIENTS: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin). MEASUREMENTS: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations. RESULTS: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P<0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P<0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P<0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P<0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P<0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P<0.025). CONCLUSIONS: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

Subdiffusion and localization in the one-dimensional trap model.

We study a one-dimensional generalization of the exponential trap model using both numerical simulations and analytical approximations. We obtain the asymptotic shape of the average diffusion front in the subdiffusive phase. Our central result concerns the localization properties. We find the dynamical participation ratios to be finite, but different from their equilibrium counterparts. Therefore, the idea of a partial equilibrium within the limited region of space explored by the walk is not exact, even for long times where each site is visited a very large number of times. We discuss the physical origin of this discrepancy, and characterize the full distribution of dynamical weights. We also study two different two-time correlation functions, which exhibit different aging properties: one is "sub aging" whereas the other one shows "full aging," therefore, two diverging time scales appear in this model. We give intuitive arguments and simple analytical approximations that account for these differences, and obtain new predictions for the asymptotic (short-time and long-time) behavior of the scaling functions. Finally, we discuss the issue of multiple time scalings in this model.

Linear and nonlinear response in the aging regime of the one-dimensional trap model.

We investigate the behavior of the response function in the one-dimensional trap model using scaling arguments that we confirm by numerical simulations. We study the average position of the random walk at time t(w)+t, given that a small bias h is applied at time t(w). Several scaling regimes are found, depending on the relative values of t, t(w), and h. Comparison with the diffusive motion in the absence of bias allows us to show that the fluctuation-dissipation relation is valid even in the aging regime, at least for times such that linear response is obeyed. However, for sufficiently long times, the response always becomes nonlinear in h.

Pictorial cues and three-dimensional information processing in early infancy.

Adults derive 3-D information from 2-D images by initially processing local line junction cues and then combining information from many junctions. Prior research indicates that 3-month-olds are sensitive to 3-D cues in individual line junctions. In Experiment 1, we examined whether infants are sensitive to holistic combinations of line junctions that adults use to derive overall 3-D structure. Infants detected a misoriented shape in an array depicting 3-D blocks but not in 2-D patterns that contained all of the trilinear junctions of the 3-D shapes but without the connecting lines. Thus, like adults, infants exhibited sensitivity to holistic combinations of line junctions rather than to individual junctions. In Experiment 2, when confronted with two test patterns, one containing an individual novel element among 15 familiar elements and the other containing a single familiar element among 15 novel elements, infants preferred to look at the former pattern in the 3-D condition but at the latter pattern in the 2-D condition. Thus, akin to pop-out in adults, discrepancies in 3-D cues selectively engaged infants' attention. These results suggest that 3-month-olds are not only sensitive to holistic combinations of line junctions that adults use to derive 3-D information but also selectively attend to these 3-D cues in static images.

Gastric emptying is accelerated in obese type 2 diabetic patients without autonomic neuropathy.

OBJECTIVE: To clarify the impact of type 2 diabetes mellitus on the gastric emptying rate. MATERIAL AND METHODS: Using a double-isotope scintigraphic technique, we assessed the gastric emptying of a standard liquid-solid meal in 13 obese type 2 diabetic patients without autonomic neuropathy (age: 47.4 +/- 8.6 yr, body mass index: 33.9 +/- 4.8 kg/m(2), glycaemia: 9.1 +/- 2.6 mmol/l) and in 7 controls with similar sex ratio, age, BMI and body fat distribution. RESULTS: The half gastric emptying time for the liquid phase was not significantly different between diabetic patients and controls (respectively: 52.7 +/- 14.5 min and 63.1 +/- 15.2 min). However, the half gastric emptying time for the solid phase was significantly shortened in diabetic patients versus controls (respectively 88.8 +/- 23.2 min in diabetic patients and 113.6 +/- 26.9 min in controls; p<0.04). Furthermore, a negative relationship was highlighted between the half gastric emptying time for the solid phase and basal glycaemia (r=-0.65, p<0.02) in diabetic patients. No significant relationship was found between gastric emptying parameters and cardiac autonomic nerve function, insulin or gastrin levels. CONCLUSION: Solid gastric emptying is accelerated in obese type 2 diabetic patients without patent autonomic neuropathy when compared to obese non diabetic patients.

Maternally inherited diabetes and deafness: a multicenter study.

BACKGROUND: Maternally inherited diabetes and deafness (MIDD), which is seen in 0.5% to 2.8% of patients with type 2 diabetes mellitus, is related to a point mutation at position 3243 of mitochondrial (mt) DNA. Its clinical description is incomplete. OBJECTIVE: To study the clinical presentation and complications of diabetes in patients with MIDD and to identify clinical characteristics that may help select diabetic patients for mtDNA mutation screening. DESIGN: Multicenter prospective descriptive study. SETTING: 16 French departments of internal medicine, diabetes and metabolic diseases, or both. PATIENTS: 54 patients with type 2 diabetes mellitus and the mtDNA 3243 mutation. MEASUREMENTS: Characteristics of diabetes, metabolic control (glycosylated hemoglobin level), complications of diabetes, and involvement of other organs. RESULTS: On average, patients with MIDD were young at diabetes onset and presented with a normal or low body mass index. None were obese. Seventy-three percent of probands had a maternal family history of diabetes. Diabetes was non-insulin-dependent at onset in 87% of patients; however, 46% of patients had non-insulin-dependent disease at onset but progressed to insulin therapy after a mean duration of approximately 10 years. Neurosensory hearing loss was present in almost all patients. Eighty-six percent of patients who received an ophthalmologic examination had macular pattern dystrophy (a specific retinal lesion). Forty-three percent of patients had myopathy, 15% had cardiomyopathy, and 18% (9 of 51) had neuropsychiatric symptoms. Although the prevalence of diabetic retinopathy was 8% among patients who received an ophthalmologic examination, lower than expected after a mean 12-year duration of diabetes, prevalence of kidney disease was 28%. This suggests that a specific renal involvement was the result of mitochondrial disease. CONCLUSIONS: Maternally inherited diabetes and deafness has a specific clinical profile that may help identify diabetic patients for mtDNA testing.