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Treatment of tibial pseudarthrosis secondary to snake bite in pediatric age: Chaaria mission hospital collaborative experience

In developing countries snake bites can cause necrosis and osteomyelitis, with consequent deformities, especially in children. Tibial segmental defects represent a therapeutic challenge, and are mainly due to congenital anomalies (agenesis or pseudoarthrosis), infections, post-traumatic fractures, and neoplastic lesions (6). A 13 years old girl was brought to our attention due to a severe deformity of left leg, secondary to previous osteomyelitis caused by a snake bite. The deformity was treated by osteotomy with peroneal excision and tibial synthesis with a DCP (Dynamic Compression Plate) which allowed to recover the right axis and joint rotation, allowing for a next step

Diet Induced Obesity Alters Intestinal Cytoplasmic Lipid Droplet Morphology and Proteome in the Postprandial Response to Dietary Fat

Dietary fat absorption by the small intestine is an efficient, multistep process that regulates the uptake and delivery of essential nutrients and energy. Fatty acids taken up by enterocytes, the absorptive cells of the small intestine, are resynthesized into triacylglycerol (TAG) and either secreted in chylomicrons or temporarily stored in cytoplasmic lipid droplets (CLDs). Proteins that associate with CLDs are thought to regulate the dynamics of TAG storage and mobilization. It is currently unclear what effect diet induced obesity (DIO) has on the balance between dietary fat storage and secretion. Specifically, there is limited knowledge of how DIO affects the level and diversity of proteins that associate with CLDs and regulate CLD dynamics. In the current study, we characterize CLDs from lean and DIO mice through histological and proteomic analyses. We demonstrate that DIO mice have larger intestinal CLDs compared to lean mice in response to dietary fat. Additionally, we identified 375 proteins in the CLD fraction isolated from enterocytes of lean and DIO mice. We identified a subgroup of lipid related proteins that are either increased or unique to the DIO CLD proteome. These proteins are involved in steroid synthesis, TAG synthesis, and lipolysis. This analysis expands our knowledge of the effect of DIO on the process of dietary fat absorption in the small intestine (D’Aquila, 2016)

HIV-1 RNA Levels and Antiretroviral Drug Resistance in Blood and Non-Blood Compartments from HIV-1–Infected Men and Women enrolled in AIDS Clinical Trials Group Study A5077

Background: Detectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART) in the AIDS Clinical Trials Group (ACTG) 5077 study. Methods: Blood, saliva and genital-secretions (compartment fluids) were collected from HIV-infected adults (≥13 years) at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL) ≥2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher’s and McNemar’s exact tests to compare VL between sexes and among compartments. Results: Samples were available for 143 subjects; 36% treated (23 men, 29 women) and 64% ‘untreated’ (40 men, 51 women). RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001). A higher proportion of men had genital shedding versus women (78% versus 41%), and RNA detection was more frequent in saliva versus genital-secretions in women when adjusted for censoring at the limit of assay detection. Inter-compartment fluid VL concordance was low in both sexes. In 22 (13 men, 9 women) paired plasma-genital-secretion genotypes from treated subjects, most had detectable resistance in both plasma (77%) and genital-secretions (68%). Resistance discordance was observed between compartments in 14% of subjects. Conclusions: HIV shedding and drug resistance detection prior to initiation/change of ART in ACTG 5077 subjects differed among tissues and between sexes, making the gold standard blood-plasma compartment assessment not fully representative of HIV at other tissue sites. Mechanisms of potential sex-dependent tissue compartmentalization should be further characterized to aid in optimizing treatment and prevention of HIV transmission. Trial Registration ClinicalTrials.gov NCT0000748

Border Terriers under primary veterinary care in England: demography and disorders

The Border Terrier is a working terrier type that is generally considered to be a relatively healthy and hardy breed. This study aimed to characterise the demography and common disorders of Border Terriers receiving veterinary care in England using de-identified electronic patient record data within the VetCompass™ Programme

Monitoring the last Apennine glacier: recent in situ campaigns and modelling of Calderone glacial apparatus

The Calderone glacier is at present the most southern glacier in Europe (42° 28' 15’’ N). The little apparatus (about 20.000 m2 in surface area) has been giving an interesting response both to short- and long-term climatic variations which resulted in a considerable reduction in surface area and volume. The glacial apparatus is split into two ice bodies (glacierets) since 2000. The two glacierets are located in a deep northward valley below the top of the Corno Grande (2912 m asl) in the centre of the Gran Sasso d’Italia mountain range (Central Italy). Such glacial apparatus has been subjected to a strong reduction, with a loss of total surface area of about 50% and thickness of about 65%with respect to the hypothetical size (about 105.00 m2 and 55 m at the Little Ice Age). Since early 90s the Calderone glacier has been subjected to several multidisciplinary field campaigns to monitor and evaluate its role as an environmental indicator in the framework of global warming. Starting from historical series related to more than a century of records, the variability of the different glacier properties has been estimated by using classical geomorphologic methods as well as in situ and remote sensing techniques. In particular, the last field campaigns, in 2015, 2016 and 2019, have been carried out using Ground Penetrating Radar equipped with different antenna frequencies, drone-based survey, snow pit measurements and chemical-physical sampling. The measurement campaigns have been complemented by a regional climate analysis, spanning the last fifty years, and snowpack modelling initialized with microphysical snow data (e.g., snow density, crystal shape and size, hardness). The snowpack chemical analyses include the main and trace elements, soluble inorganic and organic ions, EC/OC and PAH, with different spatial resolution depending on the analytes. We present here the methodological approach used and some preliminary results

Long Term Assessment of Anti-SARS-CoV-2 Immunogenicity after mRNA Vaccine in Persons Living with HIV

(1) Background: Waning of neutralizing and cell-mediated immune response after the primary vaccine cycle (PVC) and the first booster dose (BD) is of concern, especially for PLWH with a CD4 count ≤200 cells/mm3. (2) Methods: Neutralizing antibodies (nAbs) titers by microneutralization assay against WD614G/Omicron BA.1 and IFNγ production by ELISA assay were measured in samples of PLWH at four time points [2 and 4 months post-PVC (T1 and T2), 2 weeks and 5 months after the BD (T3 and T4)]. Participants were stratified by CD4 count after PVC (LCD4, ≤200/mm3; ICD4, 201–500/mm3, and HCD4, &gt;500/mm3). Mixed models were used to compare mean responses over T1–T4 across CD4 groups. (3) Results: 314 PLWH on ART (LCD4 = 56; ICD4 = 120; HCD4 = 138) were enrolled. At T2, levels of nAbs were significantly lower in LCD4 vs. ICD4/HCD4 (p = 0.04). The BD was crucial for increasing nAbs titers above 1:40 at T3 and up to T4 for WD614G. A positive T cell response after PVC was observed in all groups, regardless of CD4 (p = 0.31). (4) Conclusions: Waning of nAbs after PVC was more important in LCD4 group. The BD managed to re-establish higher levels of nAbs against WD614G, which were retained for 5 months, but for shorter time for Omicron BA.1. The T cellular response in the LCD4 group was lower than that seen in participants with higher CD4 count, but, importantly, it remained above detectable levels over the entire study period

Identification, replication and characterization of epigenetic remodelling in the aging genome:A cross population analysis

Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in a large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs and replicated them in two independent Danish cohorts. The double-replicated CpGs were characterized by distribution over gene regions and location in relation to CpG islands. The replicated CpGs were further characterized by involvement in biological pathways to study their functional implications in aging. We identified 67,604 age-associated CpG sites reaching genome-wide significance of FWE

The N137 and P140 amino acids in the p51 and the P95 amino acid in the p66 subunit of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase are instrumental to maintain catalytic activity and to design new classes of anti-HIV-1 drugs

Amino acids N137 and P140 in the p51 subunit of HIV-1 reverse transcriptase (RT) are part of the beta 7-beta 8-loop that contributes to the formation of the base of the non-nucleoside RT inhibitor (NNRTI)-binding pocket and makes up a substantial part of the dimerization interface. Amino acid P95 in p66 also markedly contributes to the dimerization binding energy. Nine RT mutants at amino acid 137 were constructed bearing the mutations Y, K, T, D, A, Q, S, H or E. The prolines at amino acid positions 95 and 140 were replaced by alanine in separate enzymes. We found that all mutant RT enzymes showed a dramatically decreased RNA-dependent DNA polymerase activity. None of the mutant RT enzymes showed marked resistance against any of the clinically used NNRTIs but they surprisingly lost significant sensitivity for NRTIs such as ddGTP. The denaturation analyses of the mutant RTs by urea are suggestive for a relevant role of N137 in the stability of the RT heterodimer and support the view that the beta 7-beta 8 loop in p51 is a hot spot for RT dimerization and instrumental for efficient polymerase catalytic activity. Consequently, N137 and P140 in p51 and P95 in p66 should be attractive targets in the design of new structural classes of RT inhibitors aimed at compromising the optimal interaction of the beta 7-beta 8 loop in p51 at the p66/p51 dimerization interface. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

Genotypic resistance testing in HIV by arrayed primer extension

The analysis of mutations that are associated with the occurrence of drug resistance is important for monitoring the antiretroviral therapy of patients infected with human immunodeficiency virus (HIV). Here, we describe the establishment and successful application of Arrayed Primer Extension (APEX) for genotypic resistance testing in HIV as a rapid and economical alternative to standard sequencing. The assay is based on an array of oligonucleotide primers that are immobilised via their 5′-ends. Upon hybridisation of template DNA, a primer extension reaction is performed in the presence of the four dideoxynucleotides, each labelled with a distinct fluorophore. The inserted label immediately indicates the sequence at the respective position. Any mutation changes the colour pattern. We designed a microarray for the analysis of 26 and 33 codons in the HIV protease and reverse transcriptase, respectively, which are of special interest with respect to drug resistance. The enormous genome variability of HIV represents a big challenge for genotypic resistance tests, which include a hybridisation step, both in terms of specificity and probe numbers. The use of degenerated oligonucleotides resulted in a significant reduction in the number of primers needed. For validation, DNA of 94 and 48 patients that exhibited resistance to inhibitors of HIV protease and reverse transcriptase, respectively, were analysed. The validation included HIV subtype B, prevalent in industrialised countries, as well as non-subtype B samples that are more common elsewhere