A retrospective evaluation of heparin product reactions in patients with alpha-gal allergies

BackgroundAlpha-gal allergy, also known as red meat allergy or alpha-gal syndrome, can present after bites of certain tick species that contain galactose-alpha-1,3-galactose (alpha-gal) carbohydrate. Following this exposure, patients may develop an allergic reaction after mammalian meat consumption. Some heparin products are derived from porcine intestinal tissue, and it is therefore possible that administering these medications to a patient with an alpha-gal allergy may trigger a reaction.ObjectiveThe purpose of this study was to evaluate the incidence of reactions to porcine heparin products in patients with an alpha-gal allergy.MethodsA retrospective case series was conducted by review of electronic medical record data. Patients included were between the ages of 18 and 89 years, with a documented alpha-gal or red meat allergy and an admission to a hospital in the Sentara Healthcare system. The primary outcome was the incidence of allergic reactions upon exposure to heparin products in patients with a documented alpha-gal allergy.ResultsPatients with a documented alpha-gal allergy received a heparin product in 57 of 158 hospital visits (36.1%). Heparin products were tolerated in 56 of the 57 visits (98.3%). The incidence of an alpha-gal reaction to unfractionated heparin was 2.6% (1/39) while the incidence of an alpha-gal reaction to enoxaparin was 0% (0/22).Conclusion and RelevanceHeparin products were associated with a low incidence of alpha-gal reactions among patients with documented alpha-gal allergy. It is possible that enoxaparin poses less of a risk for reaction in these patients compared to unfractionated heparin.     

An Exploratory Network Analysis of Sexual and Relationship Satisfaction Comparing Partnered Cisgendered Men and Women

BackgroundSexual and relationship satisfaction are intimately connected and share many predictors.AimThe aim of the present study is to disentangle the relationship between sexual and relationship satisfaction, by exploring the connections to other relevant correlates.MethodsRegularized mixed graphical model networks were estimated separately for men and women, which were compared using the network comparison test. In addition, strength centrality and community structure were explored.OutcomeThe partial correlation structure between sexual satisfaction, relationship satisfaction and their correlates.ResultsThe associations between variables measuring sexual and relationship satisfaction and related constructs did not differ significantly between partnered, cisgendered men and women. Sexual and relationship satisfaction were associated with sexual pleasure, sexual distress, and sexual communication for both men and women. Sexual satisfaction was the most central variable in the network for men (strength = 1.1), while sexual desire was the most central variable for women (strength = 1.1). Frequency of sexual activity was a central variable for both men and women (strength men = 1.0, strength women = 1.1). The community analysis showed similar communities of variables for men and women, except that frequency of sexual activity consistently belonged to the same community as sexual and relationship satisfaction for men, but not as consistently for women.Clinical TranslationThe results have clinical implication in sex and couples therapy, as they increase the knowledge on sexual and relationship satisfaction.Strengths & LimitationsA strength of the study is the population-based dataset, and a limitation is that inferences of causality cannot be made due to the cross-sectional study design.ConclusionThe present study suggests that men and women are largely similar when comparing constructs related to sexual and relationship satisfaction.Nickull S, Källström M, Jern P. An Exploratory Network Analysis of Sexual and Relationship Satisfaction Comparing Partnered Cisgendered Men and Women. J Sex Med 2022;19:711–718.     

Fatal cases of bovine anaplasmosis in a herd infected with different Anaplasma marginale genotypes in southern Spain

The genus Anaplasma contains various species capable of causing disease in animals and humans. Anaplasma marginale is one of the main tick-borne pathogens of bovines in tropical and subtropical regions; however, these bacteria are now being detected more frequently in other regions of the world including Europe. In July 2017, abortions, mortality and morbidity in Retinta breed of cattle were investigated in southwestern Spain. Based on clinical signs, the provisional clinical diagnosis of bovine anaplasmosis was made. A molecular-phylogenetic approach was used to characterize A. marginale using multiple markers, including 16S rRNA, msp1a, msp4 and msp5 genes. The msp1α sequence was different from the previously described sequences from Spain as well as other countries. The isolates of A. marginale were classified as Genotype C, with two of the five tandem repeats in the amino acid sequences MSP1α being novel. The highest variability was observed in the four sequences of msp5 which was depicted in their clustering into multiple clades on a phylogenetic tree. Comparison of msp5 nucleotide sequences and the corresponding amino acid sequences revealed the co-existence of different strains in the same region. This study highlights the occurrence of clinical bovine anaplasmosis in an endemic region of Spain.     

Efficacy of stem cell-based therapies for colistin-induced nephrotoxicity

The increase in infections with multidrug resistant bacteria has forced to return to the use of colistin, antibiotic with known nephrotoxicity. Mesenchymal stem cells (MSCs) are being extensively investigated for their potential in regenerative medicine. This study aimed to investigate the possible protective mechanisms of the MSCs against kidney injury induced by colistin. Forty adult female albino rats were randomly classified into 4 equal groups; the control group, the MSC-treated group (a single dose of 1 ×10⁶ /ml MSCs through the tail vein), the colistin-treated group (36 mg/kg/day colistin was given for 7 days), and the both colistin and MSC group (36 mg/kg/day colistin and 1 ×10⁶ /ml MSCs). Main outcome measures were histopathological alterations, kidney malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and immunohistological autophagy evaluation. MSC repressed the progression of colistin-induced kidney injury as evidenced by the improvement of histopathological alterations and the substantial increase MDA, and decrease SOD and CAT in serum levels. Moreover, MSC resulted in a profound reduction in oxidative stress as manifested by decreased MDA and increased SOD in serum. Notably, MSC suppressed colistin-induced autophagy; it reduced renal levels of Beclin-1, P62 and LC3A/B. Furthermore, MSC decreased renal levels of eNOS. Lastly, MSC efficiently decreased expression of the TUNEL positive cell number. MSC confers protection against colistin-induced kidney injury by alleviating oxidative stress, nitric oxide synthase besides modulating reducing autophagy and apoptosis.     

MMV020275 and MMV020490, promising compounds from malaria box for the treatment of equine piroplasmosis

Equine piroplasmosis is a tick-transmitted disease that is considered one of the most serious infectious diseases affecting equines. Searching for novel antipiroplasm drugs remains indispensable due to the emergence and spreading of resistant piroplasm parasites against the limited currently used drugs, diminazene aceturate and imidocarb dipropionate. Therefore, novel drugs with specified targets need to be identified and exploited. The inhibitory effects of Medicines for Malaria Venture (MMV) Malaria Box compounds with potent in vitro anti-equine piroplasmosis activity were evaluated against the growth of B. microti in mice in this study. Using a nested PCR assay targeting the B. microti ss-rRNA gene, we investigated the far-reaching impacts of effective combinations to inhibit parasite recrudescence. Using real-time PCR, this study revealed potential targets for the found potent compounds. When used as monotherapy, screening the Malaria Box against the in vivo growth of the B. microti parasite resulted in the discovery of new, potent antipiroplasm medicines, such as MMV020275 and MMV020490. In MMV020275-treated Theileria equi in vitro culture, a statistically significant difference (P<0.05) in the cGMP-dependent protein kinase (PKG) mRNA level was identified as a down-regulation in contrast to non-treated cultures. In conclusion, new potent antipiroplasm drugs, including MMV020275 and MMV020490 are identified. MMV020275 significantly down-regulate the mRNA levels of the PKG gene. Clofazimine enhanced the inhibitory efficacy of MMV compounds which is suggested to use in treatment of animal or human babesiosis in the future.     

Survival in the understorey: Testing direct and indirect effects of microclimatological changes on Ixodes ricinus

The distribution of ticks in the Ixodes ricinus species complex is partly driven by climate, with temperature and relative humidity affecting survival. These variables are driven by macroclimate, but vary locally due to microclimate buffering. This buffering has been suggested to be one of the driving forces behind variation in tick survival and density in time and space. In order to understand the role of the herb layer with respect to this variation, we deployed I. ricinus within an existing experimental setup studying the response of forest understorey to micrometeorological changes. This allowed for the analysis of both direct effects of warming on tick survival in controlled field conditions, as well as indirect effects through changes in herb layer biomass. Herb layer biomass estimates were observed to be higher in plots that had been experimentally warmed, with a trend towards higher survival in these warmed plots. This marginal increase in survival rate may be due to increased microclimate buffering. Comparing our results to literature implies that canopy and shrub layer vegetation have a larger effect on climate buffering, and therefore also on tick survival. Since the herb layer biomass is expected to increase due to global warming and increased frequency of disturbance-induced canopy gaps, survival in forested habitats may increase in the future. This would increase the difference in survival compared to that in open habitats.     

In Vivo Evaluation of Nanoemulsion Formulations for Metformin and Repaglinide Alone and Combination

Repaglinide and Metformin are used to treat Type 2 diabetes. Repaglinide with poor water solubility has relatively low oral bioavailability (56%) and undergoes hepatic first-pass metabolism. The oral bioavailability of metformin HCl is also low (about 50-60%). The purpose of this study was to prepare nanoemulsion formulations containing metformin HCl or repaglinide alone or in combination and characterize them in vitro and in vivo. Nanoemulsion formulations containing metformin HCl and/or repaglinide were successfully prepared and in vitro characterized. In addition, in vivo efficacy of nanoemulsion formulations was evaluated in a streptozotocin-nicotinamide-induced diabetic rat model. Biochemical, histopathological, and immunohistochemical evaluations were also performed. The mean droplet size and zeta potential values of nanoemulsion formulations were in the range of 110.15±2.64-120.23±2.16 nm and -21.95 – -24.33 mV, respectively. The percent entrapment efficiency values of nanoemulsion formulations were in the range of 93.600%-96.152%. All nanoemulsion formulations had a PDI of ≤0.223. A statistically significant decrease was observed in the blood glucose values of the diabetic rats treated with nanoemulsion formulations containing active substance/substances, compared to diabetic rats (control) (p<0.05). Nanoemulsion formulations (especially nanoemulsion containing metformin HCl and repaglinide combination) have a better antidiabetic activity and are more effective in reducing oxidative stress caused by diabetes.