Time to Get Help? Help-Seeking Process in Latin American Hospital Patients with Alcohol Use Disorder

International Journal of Mental Health and Addiction - Alcohol Use Disorder (AUD) is one of the most harmful conditions associated with consumption. Despite a high level of consumption and an...     

In vivo bracket bond strength using two adhesive systems applied under wet and dry conditions

The purpose of this study was to investigate, in vivo, the bond strength of two adhesive materials: a moisture insensitive primer (MIP)* and a one step self etching primer (SEP)*, both used with Transbond XT* on dry and wet enamel and an adhesion time of 10-15 minutes. First or second upper and/or lower bicuspids (n = 124), to be extracted for orthodontic reasons, were used. A comparison of the materials' behavior was conducted under four different situations: 1) MIP on enamel etched and dry; 2) MIP on a surface etched and wetted with patient's saliva; 3) SEP on a dry field, 4) SEP on a saliva-wet enamel. For statistical analysis, Dunn-Sidak's multiple comparison test was applied with a probability of less than 0.05 (before correction). Stainless steel brackets with mesh-backed pads were bonded to the teeth. Bond strength was tested with modified orthodontic pliers on which a strain-gage was fixed to measure handle deformation while debonding. Moisture insensitive primer tested on wet enamel showed the highest mean bond strength outcomes (8.98 MPa) compared to one step etching primer (5.81 MPa). Statistical difference between these groups was significant (p = 0.000). Standard deviation was lower for the one-step technique, under dry and wet conditions. Since the media bond strength of SEP proved sufficient for clinical purposes and its behavior tended to be more homogeneous, this was considered the best choice.     

Isolation and synthesis of cryptosanguinolentine (isocryptolepine), a naturally-occurring bioactive indoloquinoline alkaloid

Cryptosanguinolentine (isocryptolepine) is one of the minor naturally-occurring monomeric indoloquinoline alkaloids, isolated from the West African climbing shrub Cryptolepis sanguinolenta. The natural product displays such a simple and unique skeleton, which chemists became interested in well before it was found in Nature. Because of its structure and biological activity, the natural product has been targeted for synthesis on numerous occasions, employing a wide range of different strategies. Hence, discussed here are aspects related to the isolation of isocryptolepine, as well as the various approaches toward its total synthesis.

The isolation and properties of the heterocycle are detailed and the diversity of chemical approaches toward the natural product are systematically ordered and reviewed.     

Characterization of a Caenorhabditis elegans glc seven-like phosphatase (gsp) orthologue from Haemonchus contortus (Nematoda)

A full-length complementary DNA (cDNA; designated Hc-stp-1) encoding a serine/threonine phosphatase (Hc-STP-1) was isolated from Haemonchus contortus, a strongylid nematode parasite of small ruminants. Hc-stp-1 was shown to be transcribed in males of both adults and fourth-stage larvae, but not in females, early larval stages or eggs. The full-length gene (2854 bp) contained ten exons and nine introns, and encoded a cDNA of 951 bp. Comparisons of the conceptually translated protein (316 amino acids, estimated at ～35 kDa) with serine/threonine phosphatases (STPs) from other organisms revealed the presence of the conserved motif LRGNHE. Structural analysis, by comparative modelling, confirmed strict conservation of residues and features involved in catalytic activity, and variation in the ligand-binding interface. Phylogenetic analysis of amino acid sequence data revealed that Hc-STP-1 clustered with STPs from other nematodes (including Caenorhabditis elegans, Trichostrongylus vitrinus, Oesophagostomum dentatum, Ascaris suum and Brugia malayi) to the exclusion of STPs from other organisms. The protein was inferred to be most closely related to the PP1 class of STPs of C. elegans, within a group containing STPs encoded, amongst others, by the genes gsp-3 and gsp-4 in this free-living nematode. The functions of proteins GSP-3 and GSP-4 are known to be central to spermatogenesis and other male-specific processes in C. elegans. The findings from the present and previous studies support the proposal that Hc-stp-1 and its product play a significant role in reproductive and/or developmental processes in maturing or adult male H. contortus.     

Preclinical dose-finding study with a liver-tropic, recombinant AAV-2/8 vector in the mouse model of galactosialidosis

Galactosialidosis (GS) is a lysosomal storage disease linked to deficiency of the protective protein/cathepsin A (PPCA). Similarly to GS patients, Ppca-null mice develop a systemic disease of the reticuloendothelial system, affecting most visceral organs and the nervous system. Symptoms include severe nephropathy, visceromegaly, infertility, progressive ataxia, and shortened life span. Here, we have conducted a preclinical, dose-finding study on a large cohort of GS mice injected intravenously at 1 month of age with increasing doses of a GMP-grade rAAV2/8 vector, expressing PPCA under the control of a liver-specific promoter. Treated mice, monitored for 16 weeks post-treatment, had normal physical appearance and behavior without discernable side effects. Despite the restricted expression of the transgene in the liver, immunohistochemical and biochemical analyses of other systemic organs, serum, and urine showed a dose-dependent, widespread correction of the disease phenotype, suggestive of a protein-mediated mechanism of cross-correction. A notable finding was that rAAV-treated GS mice showed high expression of PPCA in the reproductive organs, which resulted in reversal of their infertility. Together these results support the use of this rAAV-PPCA vector as a viable and safe method of gene delivery for the treatment of systemic disease in non-neuropathic GS patients.     

At-risk brain tissue identified with arterial spin labeling in neurotuberculosis

A 13-year-old immunocompromised girl developed neurotuberculosis. Arterial spin labeling technique indicated areas of hypoperfusion in the vascular territories of the left posterior cerebral artery and superior cerebellar artery without restricted diffusion, suggesting early tuberculous arteritis. MR angiography confirmed vascular involvement, so adjunctive anticoagulant therapy was initiated. Complete resolution of arterial spin labeling findings was observed 1 month later. This documents early tuberculous vasculopathy revealed by arterial spin labeling in a child with neurotuberculosis. Since there may be a paucity of clinical symptoms in the evolution of arteritis in neurotuberculosis, arterial spin labeling may help indicate early hypoperfusion and alert for modification of treatment before irreversible vascular damage occurs.     

In vitro sulfate turnover in osteogenesis imperfecta congenita and tarda

Sulfate (³⁵SO₄^?2) uptake was studied in confluent skin fibroblasts from three patients with osteogenesis imperfecta “congenita,” six patients with osteogenesis imperfecta “tarda,” three clinically unaffected relatives of an osteogenesis imperfecta tarda patient, and four controls. Only two of the osteogenesis imperfecta congenita cell strains showed an increased uptake of sulfate, all other cell strains being comparable to the control group. The degradation rate of glycosaminoglycans in mutants as seen by the chase experiments was comparable to that found in the normal control cell strains. Glucose oxidation was normal in the osteogenesis imperfecta cell strains having an abnormal sulfate uptake. This rules out the possibility of an hypermetabolic state of these cells. These findings do not warrant the use of ³⁵SO₄^?2 incorporation in cultured cells as a tool for prenatal diagnosis of osteogenesis imperfecta.