Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way.

The first stars are predicted to have formed within 200 million years after the Big Bang, initiating the cosmic dawn. A true first star has not yet been discovered, although stars with tiny amounts of elements heavier than helium ('metals') have been found in the outer regions ('halo') of the Milky Way. The first stars and their immediate successors should, however, preferentially be found today in the central regions ('bulges') of galaxies, because they formed in the largest over-densities that grew gravitationally with time. The Milky Way bulge underwent a rapid chemical enrichment during the first 1-2 billion years, leading to a dearth of early, metal-poor stars. Here we report observations of extremely metal-poor stars in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than the solar value without noticeable carbon enhancement. We confirm that most of the metal-poor bulge stars are on tight orbits around the Galactic Centre, rather than being halo stars passing through the bulge, as expected for stars formed at redshifts greater than 15. Their chemical compositions are in general similar to typical halo stars of the same metallicity although intriguing differences exist, including lower abundances of carbon.

Early initiation of combined antiretroviral therapy preserves immune function in the gut of HIV-infected patients.

Massive loss of lamina propria CD4(+) T cells, changes in the lymphatic architecture, and altered intestinal epithelial barrier leading to microbial translocation are the common features of HIV-1 infection and are not fully restored under combined antiretroviral therapy (cART). To better understand determinants of gut mucosal restoration, we have performed phenotypic and gene expression analyses of the gut from HIV-infected patients, naive or treated with cART initiated either at the early phase of the primary infection or later during the chronic phase. We found a depletion of T helper type 22 (Th22) and interleukin-17-producing cells in naive patients. These populations, except Th22 cells, were not restored under cART. Regulatory T cells/Th17 ratio was significantly increased in HIV-infected patients and was inversely correlated to the restoration of CD4(+) T cells but not to gut HIV DNA levels. Gene profile analysis of gut mucosal distinguished two groups of patients, which fitted with the timing of cART initiation. In their majority early, but not later treated patients, exhibited conserved intestinal lymphoid structure, epithelial barrier integrity and dendritic cell maturation pathways. Our data demonstrate that early initiation of cART helps to preserve and/or restore lymphoid gut mucosal homeostasis and provide a rationale for initiating cART during the acute phase of HIV infection.

A single low-energy, iron-poor supernova as the source of metals in the star SMSS J031300.36-670839.3.

The element abundance ratios of four low-mass stars with extremely low metallicities (abundances of elements heavier than helium) indicate that the gas out of which the stars formed was enriched in each case by at most a few--and potentially only one--low-energy supernova. Such supernovae yield large quantities of light elements such as carbon but very little iron. The dominance of low-energy supernovae seems surprising, because it had been expected that the first stars were extremely massive, and that they disintegrated in pair-instability explosions that would rapidly enrich galaxies in iron. What has remained unclear is the yield of iron from the first supernovae, because hitherto no star has been unambiguously interpreted as encapsulating the yield of a single supernova. Here we report the optical spectrum of SMSS J031300.36-670839.3, which shows no evidence of iron (with an upper limit of 10(-7.1) times solar abundance). Based on a comparison of its abundance pattern with those of models, we conclude that the star was seeded with material from a single supernova with an original mass about 60 times that of the Sun (and that the supernova left behind a black hole). Taken together with the four previously mentioned low-metallicity stars, we conclude that low-energy supernovae were common in the early Universe, and that such supernovae yielded light-element enrichment with insignificant iron. Reduced stellar feedback both chemically and mechanically from low-energy supernovae would have enabled first-generation stars to form over an extended period. We speculate that such stars may perhaps have had an important role in the epoch of cosmic reionization and the chemical evolution of early galaxies.

Dynamics of HIV-1 DNA level in highly antiretroviral-experienced patients receiving raltegravir-based therapy.

To assess dynamics of HIV-1 DNA in highly antiretroviral (ARV)-experienced HIV-infected patients successfully treated with raltegravir (RAL)-containing therapy. Nineteen patients with virological failure whose ARV treatment was switched to a RAL-based salvage regimen with virological success were included (Group I). Ten patients in virological failure and responding to ARV salvage therapy not containing RAL were also included (Group II). The HIV-1 DNA level in peripheral blood mononuclear cells (PBMC) was assessed by real-time PCR at baseline, W12, W24, W36 or W48. In group I, a marked decrease in the HIV-1 DNA level was observed at W12 both in PBMC (median decrease = 0.38 log(10)copies/10(6)PBMC; P < 0.001) and in CD4 T cells (0.85 log(10)copies/10(6)CD4 T cells; P < 0.001). Plasma HIV-1 RNA decrease was correlated with HIV-1 DNA decrease expressed as copies/10(6)CD4 T cells (r = 0.55, P = 0.03). HIV-1 DNA level reached a steady state by W24. Thus, RAL-containing treatment in highly ARV-experienced patients was associated with a rapid HIV-1 DNA decrease, mainly in the circulating CD4 T cells compartment. Group II patients showed an early decrease in the HIV-1 DNA load until W12, which was 2.5-fold less pronounced in the CD4 T cells compartment than in the RAL-treated patients. The potent action of RAL-containing treatment observed in the CD4 T cells compartment may suggest a pronounced reduced inhibition in the pool of regenerating CD4 T cells on a RAL-based therapy.

Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy.

OBJECTIVES: Recent data showed the selection of mutations in the integrase gene, mainly involving position 148 or 155, in patients displaying virological failure (VF) on raltegravir (RAL) therapy. Here, we describe the development of RAL resistance, in both plasmatic and cellular compartments, in three heavily pretreated HIV-infected patients failing RAL-containing regimens. METHODS: Three of 17 patients receiving RAL displayed VF. The entire integrase gene, isolated from plasma and peripheral blood mononuclear cells (PBMC), was sequenced. A clonal analysis was performed in one patient at the time of VF. RESULTS: At the time of VF, RAL-resistance mutations were selected: (i) Q148R in patients 1 and 3; (ii) T66A and E92Q in patient 2. A gradual accumulation of new mutations was observed in all patients, including G140S, Q148H and N155H in patient 1, L74I in patient 2, and G140S in patient 3. Clonal analysis showed the coexistence, in patient 1, of the two common resistance pathways (mutations Q148R/H and N155H) found in distinct quasi-species. In addition, RAL-resistance mutations were detected in HIV DNA in all patients. CONCLUSIONS: Having rapidly established, resistance to RAL evolves and diversifies, and is likely to impact the efficacy of subsequently used second-generation integrase inhibitors. Moreover, RAL-resistance mutations can be archived early in PBMC.

[Renal sarcoidosis with a pseudotumoral pyelic localization]. / Sarcoïdose rénale avec localisation pyélique pseudo-tumorale.

BACKGROUND: Renal sarcoidosis exceptionally presents as a unilateral pyelic pseudotumor as in this case where it was associated with granulomatous nephropathy. CASE REPORT: A 33-year-old man had a two-year history of systemic sarcoidosis with no renal involvement. He developed renal failure related to interstitial granulomatous nephropathy associated with a pyelic localization leading to unilateral hydronephrosis. Urine drainage associated with corticosteroid therapy provided a favorable course. DISCUSSION: Renal involvement in sarcoidosis is usually the consequence of hypercalcemia and hypercalciuria related to ectopic secretion of calcitriol by the sarcoidosic granulomas, with urinary lithiasis and nephrocalcinosis leading to renal failure and also granluomatous interstitial nephropathy. Glomerulopathy or obstructive nephropathy are rarely reported. Intraluminal localizations such as the pyelic lesion in our case are exceptional but must be detected early since they respond to corticosteroid therapy.

[The treatment of old dislocations of the radial head in children by osteotomy of the upper end of the ulna. Apropos of 15 cases]. / Le traitement des luxations anciennes de la tête radiale chez l'enfant par l'ostéotomie haute du cubitus. A propos de 15 cas.

Fifteen old dislocations of the radial head in children were treated by open reduction combined with a high osteotomy of the ulna and a reconstruction of the annular ligament. This method, described by the authors in 1978, was used in nine post-traumatic, three congenital, two paralytic and one dislocation associated with multiple exostoses. Twelve children were reviewed with a follow-up of two to 11 years. Nine radial heads remained stable and well reduced. The three congenital dislocations recurred. Eight elbows showed normal alignment and the other four were only improved. Ten elbows had normal movement or better movement than before the operation. Eleven children used their elbow normally or better than before. In all, 14 children were improved, and only one elbow had unaltered function. The results obtained in congenital dislocations should be able to be improved by a number of technical precautions.

Anatomic basis of the transgluteal approach to the hip.

In order to define the technical modalities of the so-called transgluteal approach to the hip, the authors studied the structure and topography of the anatomic features encountered in this approach. The gluteus medius, gluteus minimus and vastus lateralis muscles are anatomically continuous by way of their tendinous fibers. The gluteus minimus muscle winds over the cranial and then anterolateral aspect of the capsule, to which it is bound by fibrous tracts and tendinous expansions; its terminal tendon blends its fibers with the anterior part of the tendon of the gluteus medius and enters into continuity with the superficial tendinous fibers of the anterior part of the vastus lateralis. The zone of junction of the three muscle structures is closely bound to the anterior aspect of greater trochanter. The caudal neurovascular trunk of the space between the gluteus medius and vastus lateralis is situated at a distance of 3 to 5 cm from the greater trochanter. The practical surgical implications are discussed, particularly as regards the methods of dissecting the anterior margin of the transgluteal incision, exposure of the capsule and preservation of the neurovascular pedicle, with reference to concepts published previously in studies elsewhere.