Effects of Acute Lithium Treatment on Brain Levels of Inflammatory Mediators in Poststroke Rats

Stroke is a leading cause of mortality and morbidity worldwide. Few therapeutic options with proven efficacy are available for the treatment of this disabling disease. Lithium is the gold standard treatment for bipolar disorder. Moreover, lithium has been shown to exhibit neuroprotective effects and therapeutic efficacy as a treatment of other neurological disorders. This study was undertaken to examine the effects of lithium on brain inflammatory mediators levels, fever, and mortality in postischemic stroke rats. Ischemic stroke was induced by occlusion of the mid cerebral artery (MCAO). Pretreatment with a single dose of lithium at 2 hours before MCAO induction significantly reduced the elevation in interleukin- (IL-) 6 and prostaglandin E2 levels in brain of post-MCAO rats, as compared to vehicle-treated animals. On the other hand, lithium did not affect the elevation in IL-1α, IL-10, IL-12, and tumor necrosis factor-α levels in brain of post-MCAO rats. Moreover, pretreatment with lithium did not alter post-MCAO fever and mortality. These results suggest that acute pretreatment with a single dose of lithium did not markedly affect post-MCAO morbidity and mortality in rats

The rediscovery of the putative ant social parasite Manica parasitica syn. nov. (Hymenoptera: Formicidae) reveals an unexpected endoparasite syndrome

Parasitism is ubiquitous across the tree of life, and parasites comprise approximately half of all animal species. Social insect colonies attract many pathogens, endo- and ectoparasites, and are exploited by social parasites, which usurp the social environment of their hosts for survival and reproduction. Exploitation by parasites and pathogens versus social parasites may cause similar behavioural and morphological modifications of the host. Ants possess two overlapping syndromes: the endo- and social parasite syndromes. We rediscovered two populations of the putative social parasite Manica parasitica in the Sierra Nevada, and tested the hypothesis that M. parasitica is an independently evolving social parasite. We evaluated traits used to discriminate M. parasitica from its host Manica bradleyi, and examined the morphology of M. parasitica in the context of ant parasitic syndromes. We find that M. parasitica is not a social parasite. Instead, M. parasitica represents cestode-infected M. bradleyi. We propose that M. parasitica should be regarded as a junior synonym of M. bradleyi. Our results emphasize that an integrative approach is essential for unravelling the complex life histories of social insects and their symbionts

Autonomous Tennis Ball Collector

Practicing tennis often involves hitting many tennis balls from one side of the court to the other without an opponent to hit the balls back. In training sessions like these, the task of collecting the balls is laborious when performed manually. The objective of this project is to develop a robotic tennis ball collector that can automatically collect the balls from one side of the court so that the player can rest rather than collect the balls manually. This document outlines the process of designing such a robot. Included in this report is background research, prototype, and concept modeling, along with a finalized design, and a complete timeline of our process. We will also detail the manufacturing process and the design verification. In the conclusion we will provide you with recommendations for future projects. Throughout our research, we discovered many similar products, but none met all of the customer’s requirements, thus opening a window for our product. After copious design consideration, we selected the strongest idea that satisfied our customers’ needs and are moving forward with structural modeling and preliminary analysis on it. After the structural prototype revealed issues in the design we went back to work and finalized a design that we felt confident with and still satisfied all the requirements. As seen in this report the final design utilizes structural framing materials to build the robot and allows for ease of attachment for all the electrical components. The final step in the design process was to test the verification prototype to ensure that it met all our specifications. Unfortunately, our design did not pass as many of the tests as we would have liked, and this is detailed in that section. While at the conclusion of this project, we did not complete as much as we hoped, there is a good foundation in place for the project to continue as our sponsor so desires

Cataract Surgery in Very Old Patients: A Case-Control Study

Advancements in surgical techniques and increased life expectancy have made cataract surgery more common among very old patients. However, surgical outcomes seem impaired in patients older than 90 years, especially with ocular comorbidities. A retrospective case-control study of 53 eyes of 53 very old patients (mean 92.6 ± 3.0) and 140 eyes of 140 matched patients (mean 75.2 ± 7.6) was undertaken. Groups were matched in terms of gender and systemic and ocular comorbidities. In very old patients, higher phacoemulsification energy (cumulative dissipated energy [CDE], 25.0 ± 22.4 vs. 16.1 ± 10.7, p = 0.01) and rate of intraoperative floppy iris syndrome (IFIS, 9.4% vs. 1.4%, p = 0.02) were observed compared to controls. Uncorrected (UCVA) and best-corrected distance visual acuity (BCVA) gains were significantly poorer among the very old patients than among the control at postoperative day 30 (0.20 ± 0.70 vs. 0.56 ± 0.61 logMAR, p < 0.001 and 0.27 ± 0.64 vs. 0.55 ± 0.62 logMAR, p = 0.006, respectively). Even after including CDE and IFIS as covariates, age remained an independent factor for poor visual gain at 30 days (p < 0.001). Cataract surgery in very old patients may demand more experienced surgeons due to higher nuclear density and the rates of IFIS. Expectations in visual acuity gains should be aligned with the patient’s age

Cataract Surgery in Very Old Patients: A Case-Control Study

Advancements in surgical techniques and increased life expectancy have made cataract surgery more common among very old patients. However, surgical outcomes seem impaired in patients older than 90 years, especially with ocular comorbidities. A retrospective case-control study of 53 eyes of 53 very old patients (mean 92.6 ± 3.0) and 140 eyes of 140 matched patients (mean 75.2 ± 7.6) was undertaken. Groups were matched in terms of gender and systemic and ocular comorbidities. In very old patients, higher phacoemulsification energy (cumulative dissipated energy [CDE], 25.0 ± 22.4 vs. 16.1 ± 10.7, p = 0.01) and rate of intraoperative floppy iris syndrome (IFIS, 9.4% vs. 1.4%, p = 0.02) were observed compared to controls. Uncorrected (UCVA) and best-corrected distance visual acuity (BCVA) gains were significantly poorer among the very old patients than among the control at postoperative day 30 (0.20 ± 0.70 vs. 0.56 ± 0.61 logMAR, p < 0.001 and 0.27 ± 0.64 vs. 0.55 ± 0.62 logMAR, p = 0.006, respectively). Even after including CDE and IFIS as covariates, age remained an independent factor for poor visual gain at 30 days (p < 0.001). Cataract surgery in very old patients may demand more experienced surgeons due to higher nuclear density and the rates of IFIS. Expectations in visual acuity gains should be aligned with the patient’s age

Exploring the association between serum phosphate levels and mortality in patients hospitalized with infectious diseases: a nationwide study

ObjectiveThe purpose of this study was to examine associations of serum phosphate levels with mortality, target organ damage and length of hospital stay in adults with infectious diseases hospitalized outside of the intensive care unit.MethodsThis nationwide retrospective cohort study comprised patients admitted with infections, to medical and surgical departments in eight tertiary hospitals during 2001–2020. The main exposure variable was the first serum phosphate levels at admission (up to 1 week). The analysis included multivariable logistic regression models and quantile regression.ResultsOf 126,088 patients (49% males, mean age: 69.3 years), 24,809 (19.7%) had decreased phosphate levels, 92,730 (73.5%) normal phosphate levels, and 8,549 (6.8%) elevated phosphate levels on admission. Overall- and in-hospital mortality rates were highest among those with hyperphosphatemia (74.5 and 16.4%, respectively), followed by those with normophosphatemia (57.0 and 6.6%), and lastly the hypophosphatemia group (48.7 and 5.6%); p &lt; 0.001 for all. After adjusting for confounders, the lowest predicted mortality rate was observed in the normophosphatemia group. In the multivariable model, hyperphosphatemia conferred a higher probability of target organ damage (OR [95% CI]: 2.43 [2.06–2.86]), while moderate hypophosphatemia conferred a lower probability (OR [95% CI]: 0.73 [0.65–0.82]), compared to normal phosphate levels and extreme hypophosphatemia showed a non-significant association (OR [95% CI]: 0.87 [0.57–1.28]). The associations were independent of renal failure. In a multivariable model, hyperphosphatemia was associated with a slight increase of 0.33 days in length of stay compared to normal phosphate levels.ConclusionA J-shaped relation was found between phosphate levels and prognosis in patients hospitalized with infectious diseases, regardless of their renal function

Early-onset progressive retinal atrophy associated with an IQCB1 variant in African black-footed cats (Felis nigripes)

African black-footed cats (Felis nigripes) are endangered wild felids. One male and full-sibling female African black-footed cat developed vision deficits and mydriasis as early as 3 months of age. The diagnosis of early-onset progressive retinal atrophy (PRA) was supported by reduced direct and consensual pupillary light reflexes, phenotypic presence of retinal degeneration, and a non-recordable electroretinogram with negligible amplitudes in both eyes. Whole genome sequencing, conducted on two unaffected parents and one affected offspring was compared to a variant database from 51 domestic cats and a Pallas cat, revealed 50 candidate variants that segregated concordantly with the PRA phenotype. Testing in additional affected cats confirmed that cats homozygous for a 2 base pair (bp) deletion within IQ calmodulin-binding motif-containing protein-1 (IQCB1), the gene that encodes for nephrocystin-5 (NPHP5), had vision loss. The variant segregated concordantly in other related individuals within the pedigree supporting the identification of a recessively inherited early-onset feline PRA. Analysis of the black-footed cat studbook suggests additional captive cats are at risk. Genetic testing for IQCB1 and avoidance of matings between carriers should be added to the species survival plan for captive management

Precision medicine in cats:novel niemann-pick type C1 diagnosed by whole-genome sequencing

State-of-the-art health care includes genome sequencing of the patient to identify genetic variants that contribute to either the cause of their malady or variants that can be targeted to improve treatment. The goal was to introduce state-of-the-art health care to cats using genomics and a precision medicine approach. To test the feasibility of a precision medicine approach in domestic cats, a single cat that presented to the University of Missouri, Veterinary Health Center with an undiagnosed neurologic disease was whole-genome sequenced. The DNA variants from the cat were compared to the DNA variant database produced by the 99 Lives Cat Genome Sequencing Consortium. Approximately 25× genomic coverage was produced for the cat. A predicted p.H441P missense mutation was identified in NPC1, the gene causing Niemann-Pick type C1 on cat chromosome D3.47456793 caused by an adenine-to-cytosine transversion, c.1322A>C. The cat was homozygous for the variant. The variant was not identified in any other 73 domestic and 9 wild felids in the sequence database or 190 additionally genotyped cats of various breeds. The successful effort suggested precision medicine is feasible for cats and other undiagnosed cats may benefit from a genomic analysis approach. The 99 Lives DNA variant database was sufficient but would benefit from additional cat sequences. Other cats with the mutation may be identified and could be introduced as a new biomedical model for NPC1. A genetic test could eliminate the disease variant from the population

Characterising and Predicting Haploinsufficiency in the Human Genome

Haploinsufficiency, wherein a single functional copy of a gene is insufficient to maintain normal function, is a major cause of dominant disease. Human disease studies have identified several hundred haploinsufficient (HI) genes. We have compiled a map of 1,079 haplosufficient (HS) genes by systematic identification of genes unambiguously and repeatedly compromised by copy number variation among 8,458 apparently healthy individuals and contrasted the genomic, evolutionary, functional, and network properties between these HS genes and known HI genes. We found that HI genes are typically longer and have more conserved coding sequences and promoters than HS genes. HI genes exhibit higher levels of expression during early development and greater tissue specificity. Moreover, within a probabilistic human functional interaction network HI genes have more interaction partners and greater network proximity to other known HI genes. We built a predictive model on the basis of these differences and annotated 12,443 genes with their predicted probability of being haploinsufficient. We validated these predictions of haploinsufficiency by demonstrating that genes with a high predicted probability of exhibiting haploinsufficiency are enriched among genes implicated in human dominant diseases and among genes causing abnormal phenotypes in heterozygous knockout mice. We have transformed these gene-based haploinsufficiency predictions into haploinsufficiency scores for genic deletions, which we demonstrate to better discriminate between pathogenic and benign deletions than consideration of the deletion size or numbers of genes deleted. These robust predictions of haploinsufficiency support clinical interpretation of novel loss-of-function variants and prioritization of variants and genes for follow-up studies