Varroa destructor reproduction and cell re-capping in mite-resistant Apis mellifera populations

Globalization has facilitated the spread of emerging pests such as the Varroa destructor mite, resulting in the near global distribution of the pest. In South African and Brazilian honey bees, mite-resistant colonies appeared within a decade; in Europe, mite-resistant colonies are rare, but several of these exhibited high levels of “re-capping” behavior. We studied re-capping in Varroa-naïve (UK/Australia) and Varroa-resistant (South Africa and Brazil) populations and found very low and very high levels, respectively, with the resistant populations targeting mite-infested cells. Furthermore, 54% of artificially infested A. m. capensis worker cells were removed after 10 days and 83% of the remaining infested cells were re-capped. Such targeted re-capping of drone cells did not occur. We propose that cell opening is a fundamental trait in mite-resistant populations and that re-capping is an accurate proxy for this behavior

Massive Osteolytic Lesion of the Femur after Total Knee Arthroplasty.

Various failure mechanisms have been identified in total knee arthroplasty (TKA). We hereby present one case of failure, which stands out because of its rapid and destructive progression. We report the case of a 72-year-old Caucasian female patient who developed a large bone osteolytic lesion of the femur after TKA. The patient presented to our hospital 7 years after the initial surgery, complaining of persistent knee pain. The lesion affected the distal half of the femur and, after a diagnostic workup, required a resection of 20 cm and reconstruction with a tumor prosthesis. Subsequent pathological analysis revealed a reaction to cement and prosthesis components. Periprosthetic osteolysis continues to be a major problem, and a reaction to cement and prosthesis components can be an elusive cause of TKA failure.info:eu-repo/semantics/publishedVersio

Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients

The clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is difficult, and reliable markers are highly desired. In this work we assess the value of several cerebrospinal fluid (CSF) markers for sCJD diagnosis. Within the framework of the Portuguese Epidemiological Surveillance Program for Human Prion Diseases, CSF samples from 71 patients with clinically suspected sCJD, 30 definite sCJD and 41 non-CJD patients, were analysed for the presence of 14-3-3 protein. CSF levels of tau (t-tau), and phosphorylated tau (p-tau181), S-100b and beta amyloid (Abeta42) proteins were determined. The influence of clinical and genetic characteristics on CSF markers sensitivity was also evaluated. Protein 14-3-3 was detected in 29/30 sCJD patients and 9/41 non-CJD patients. Extremely elevated t-tau and S-100b protein levels were found in sCJD patients, while p-tau181 levels were only slightly elevated and Abeta42 showed no differences compared to controls. 14-3-3 was the most sensitive parameter (97%), but its specificity was low (78%); sensitivity/specificity for other proteins were: S-100b-93/93%, t-tau-93/95%, with maximum accuracy being obtained by a combination of tests (14-3-3 combined with either t-tau or S-100b, or combining S-100b with t-tau/Abeta42 or p-tau/t-tau ratios). The sensitivity of 14-3-3, as well as of p-tau181/t-tau ratio, was decreased in younger patients with long disease duration, with the PrP-2 isotype and MV genotype. Both 14-3-3, t-tau and S-100b are sensitive markers for sCJD, but 14-3-3 specificity seems to be lower in this special clinical setting of rapidly progressing dementias. We propose that in cases with a 14-3-3 weak positive result, or in young patients with long disease duration, a second CSF marker would be valuable for the diagnosis of sCJD

Pseudohypoparathyroidism type I-b with neurological involvement is associated with a homozygous PTH1R mutation

Pseudohypoparathyroidism type 1b (PHP1b) is characterized by hypocalcemia, hyperphosphatemia, increased levels of circulating parathyroid hormone (PTH), and no skeletal or developmental abnormalities. The goal of this study was to perform a full characterization of a familial case of PHP1b with neurological involvement and to identify the genetic cause of disease. The initial laboratory profile of the proband showed severe hypocalcemia, hyperphosphatemia and normal levels of PTH, which was considered to be compatible with primary hypoparathyroidism. With disease progression the patient developed cognitive disturbance, PTH levels were found to be slightly elevated and a picture of PTH resistance syndrome seemed more probable. The diagnosis of PHP1b was established after the study of family members and blunted urinary cAMP results were obtained in a PTH stimulation test. Integration of whole genome genotyping and exome sequencing data supported this diagnosis by revealing a novel homozygous missense mutation in PTH1R (p.Arg186His) completely segregating with the disease. Here, we demonstrate segregation of a novel mutation in PTH1R with a phenotype of PHP1b presenting with neurological symptoms, but no bone defects. This case represents the extreme end of the spectrum of cognitive impairment in PTH dysfunction and defines a possible novel form of PHP1b resulting from the impaired interaction between PTH and PTH1R

Is slowness a better discriminator of disability than frailty in older adults?

Background:The trajectory of incident disability that occurs simultaneously with changes in frailty status, as well as how much each frailty component contributes to this process in the different sexes, are unknown. The objective of this study is to analyse the trajectory of the incidence of disability on basic and instrumental activities of daily living (BADL and IADL) as a function of the frailty changes and their components by sex over time. // Methods: Longitudinal analyses of 1522 and 1548 of the English Longitudinal Study of Ageing study participants without BADL and IADL disability, respectively, and without frailty at baseline. BADL and IADL were assessed using the Katz and Lawton Scales and frailty by phenotype at 4, 8, and 12 years of follow-up. Generalized mixed linear models were calculated for the incidence of BADL and IADL disability, as an outcome, using changes in the state of frailty and its components, as the exposure, by sex in models fully adjusted for sociodemographic, behavioural, biochemical, and clinical characteristics. // Results: The mean age, at baseline, of the 1522 eligible individuals free of BADL and free of frailty was 68.1 ± 6.2 years (52.1% women) and of the 1548 individuals free IADL and free frailty was 68.1 ± 6.1 years (50.6% women). Women who became pre-frail had a higher risk of incidence of disability for BADL and IADL when compared with those who remained non-frail (P < 0.05). Men and women who became frail had a higher risk of incidence of disability regarding BADL and IADL when compared with those who remained non-frail (P < 0.05). Slowness was the only component capable of discriminating the incidence of disability regarding BADL and IADL when compared with those who remained without slowness (P < 0.05). Weakness and low physical activity level in men and exhaustion in women also discriminated the incidence of disability (P < 0.05). // Conclusions: Slowness is the main warning sign of functional decline in older adults. As its evaluation is easy, fast, and accessible, screening for this frailty component should be prioritized in different clinical contexts so that rehabilitation strategies can be developed to avoid the onset of disability

CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result

Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases

Mitochondrial-dependent apoptosis in Huntington's disease human cybrids

We investigated the involvement of mitochondrial-dependent apoptosis in Huntington's disease (HD) vs. control (CTR) cybrids, obtained from the fusion of human platelets with mitochondrial DNA-depleted NT2 cells, and further exposed to 3-nitropropionic acid (3-NP) or staurosporine (STS). Untreated HD cybrids did not exhibit significant modifications in the activity of mitochondrial respiratory chain complexes I-IV or in mtDNA sequence variations suggestive of a primary role in mitochondrial susceptibility in the subpopulation of HD carriers studied. However, a slight decrease in mitochondrial membrane potential and increased formation of intracellular hydroperoxides was observed in HD cybrids under basal conditions. Furthermore, apoptotic nuclei morphology and a moderate increase in caspase-3 activation, as well as increased levels of superoxide ions and hydroperoxides were observed in HD cybrids upon 3-NP or STS treatment. 3-NP-evoked apoptosis in HD cybrids involved cytochrome c and AIF release from mitochondria, which was associated with mitochondrial Bax translocation. CTR cybrids subjected to 3-NP showed increased mitochondrial Bax and Bim levels and the release of AIF, but not cytochrome c, suggesting a different mode of cell death, linked to the loss of membrane integrity. Additionally, increased mitochondrial Bim and Bak levels, and a slight release of cytochrome c in untreated HD cybrids may help to explain their moderate susceptibility to mitochondrial-dependent apoptosi

Optimal use of visual information in adolescents and young adults with developmental coordination disorder

Recent reports offer contrasting views on whether or not the use of online visual control is impaired in individuals with developmental coordination disorder (DCD). This study explored the optimal temporal basis for processing and using visual information in adolescents and young adults with DCD. Participants were 22 adolescents and young adults (12 males and 10 females; M = 19 years, SD = 3). Half had been diagnosed with DCD as children and still performed poorly on the movement assessment battery for children (DCD group; n = 11), and half reported typical development (TD group; n = 11) and were age- and gender-matched with the DCD group. We used performance on a steering task as a measure of information processing and examined the use of advance visual information. The conditions varied the duration of advance visual information: 125, 250, 500, 750, and 1,000 ms. With increased duration of advance visual information, the TD group showed a pattern of linear improvement. For the DCD group, however, the pattern was best described by a U-curve where optimal performance occurred with about 750 ms of advance information. The results suggest that the DCD group has an underlying preference for immediate online processing of visual information. The exact timing for optimal online control may depend crucially on the task, but too much advance information is detrimental to performance

Antimicrobial activity of an L-amino acid oxidase isolated from Bothrops leucurus snake venom

Some snake venom proteins present enzymatic activities, such as L-amino acid oxidase (LAAO). The aim of this paper was to investigate the effect of Bothrops leucurus total venom (BleuTV) and its fraction LAAO (BleuLAAO) on bacteria, yeast, and promastigote forms of Leishmania amazonensis and Leishmania chagasi, and epimastigote forms of Trypanosoma cruzi. BleuTV was isolated with a Protein Pack 5PW® (Waters Corporation, USA), and several fractions were obtained. BleuLAAO was purified to high molecular homogeneity, and its N-terminal amino acid sequence shared a high degree of amino acid conservation with other LAAOs. BleuTV inhibited Staphylococcus aureus growth in a dose-dependent manner, with a minimum inhibitory concentration (MIC) of 25 &#956;g/mL, which corresponded to its minimum lethal concentration (MLC). BleuTV also inhibited the growth of promastigote forms of L. chagasi and L. amazonensis, with respective IC50 values of 1.94 &#956;g/mL and 5.49 &#956;g/mL. Furthermore, it repressed T. cruzi growth with an IC50 of 1.14 &#956;g/mL. However, BleuLAAO did not inhibit the growth of the microorganisms studied and was not toxic to macrophages. BleuTV had low toxicity against macrophages at the concentrations studied. In conclusion, whole venom from Bothrops leucurus inhibited the growth of some microorganisms, including S. aureus, Leishmania sp., and T. cruzi