Endogenous Endophthalmitis: Etiology and Treatment

This chapter comprehensively covers all aspects of endogenous endophthalmitis from systemic infectious agents, with an emphasis on reported and newer etiologies to broaden the diagnostic and investigative acumen of treating ophthalmic providers. The discussion includes the etiology of metastatic endophthalmitis and diagnostic investigations, including polymerase chain reaction (PCR), for identification of bacterial and viral infections involving the eye in both immunosuppressed in non-immunosuppressed patients. Additionally, we present clinical and diagnostic findings of fungal infections, protozoal infections, and helminthic infections. Pediatric cases are also reported and etiologies described. We discuss both etiology and diagnostic challenges. Current therapeutic modalities and outcomes are reviewed. While no two cases of metastatic endophthalmitis are the same, some similarities may exist that allow us to generalize how to approach and treat this potentially sight- and life-threatening spectrum of diseases and find the underlying systemic cause

Antipsychotic Use in Pregnancy: Patient Mental Health Challenges, Teratogenicity, Pregnancy Complications, and Postnatal Risks

Pregnant women constitute a vulnerable population, with 25.3% of pregnant women classified as suffering from a psychiatric disorder. Since childbearing age typically aligns with the onset of mental health disorders, it is of utmost importance to consider the effects that antipsychotic drugs have on pregnant women and their developing fetus. However, the induction of pharmacological treatment during pregnancy may pose significant risks to the developing fetus. Antipsychotics are typically introduced when the nonpharmacologic approaches fail to produce desired effects or when the risks outweigh the benefits from continuing without treatment or the risks from exposing the fetus to medication. Early studies of pregnant women with schizophrenia showed an increase in perinatal malformations and deaths among their newborns. Similar to schizophrenia, women with bipolar disorder have an increased risk of relapse in antepartum and postpartum periods. It is known that antipsychotic medications can readily cross the placenta, and exposure to antipsychotic medication during pregnancy is associated with potential teratogenicity. Potential risks associated with antipsychotic use in pregnant women include congenital abnormalities, preterm birth, and metabolic disturbance, which could potentially lead to abnormal fetal growth. The complex decision-making process for treating psychosis in pregnant women must evaluate the risks and benefits of antipsychotic drugs

Conservation of Human Microsatellites across 450 Million Years of Evolution

The sequencing and comparison of vertebrate genomes have enabled the identification of widely conserved genomic elements. Chief among these are genes and cis-regulatory regions, which are often under selective constraints that promote their retention in related organisms. The conservation of elements that either lack function or whose functions are yet to be ascribed has been relatively little investigated. In particular, microsatellites, a class of highly polymorphic repetitive sequences considered by most to be neutrally evolving junk DNA that is too labile to be maintained in distant species, have not been comprehensively studied in a comparative genomic framework. Here, we used the UCSC alignment of the human genome against those of 11 mammalian and five nonmammalian vertebrates to identify and examine the extent of conservation of human microsatellites in vertebrate genomes. Out of 696,016 microsatellites found in human sequences, 85.39% were conserved in at least one other species, whereas 28.65% and 5.98% were found in at least one and three nonprimate species, respectively. An exponential decline of microsatellite conservation with increasing evolutionary time, a comparable distribution of conserved versus nonconserved microsatellites in the human genome, and a positive correlation between microsatellite conservation and overall sequence conservation, all suggest that most microsatellites are only maintained in genomes by chance, although exceptionally conserved human microsatellites were also found in distant mammals and other vertebrates. Our findings provide the first comprehensive survey of microsatellite conservation across deep evolutionary timescales, in this case 450 Myr of vertebrate evolution, and provide new tools for the identification of functional conserved microsatellites, the development of cross-species microsatellite markers and the study of microsatellite evolution above the species level

Design and Implementation of Degenerate Microsatellite Primers for the Mammalian Clade

Microsatellites are popular genetic markers in molecular ecology, genetic mapping and forensics. Unfortunately, despite recent advances, the isolation of de novo polymorphic microsatellite loci often requires expensive and intensive groundwork. Primers developed for a focal species are commonly tested in a related, non-focal species of interest for the amplification of orthologous polymorphic loci; when successful, this approach significantly reduces cost and time of microsatellite development. However, transferability of polymorphic microsatellite loci decreases rapidly with increasing evolutionary distance, and this approach has shown its limits. Whole genome sequences represent an under-exploited resource to develop cross-species primers for microsatellites. Here we describe a three-step method that combines a novel in silico pipeline that we use to (1) identify conserved microsatellite loci from a multiple genome alignments, (2) design degenerate primer pairs, with (3) a simple PCR protocol used to implement these primers across species. Using this approach we developed a set of primers for the mammalian clade. We found 126,306 human microsatellites conserved in mammalian aligned sequences, and isolated 5,596 loci using criteria based on wide conservation. From a random subset of ∼1000 dinucleotide repeats, we designed degenerate primer pairs for 19 loci, of which five produced polymorphic fragments in up to 18 mammalian species, including the distinctly related marsupials and monotremes, groups that diverged from other mammals 120–160 million years ago. Using our method, many more cross-clade microsatellite loci can be harvested from the currently available genomic data, and this ability is set to improve exponentially as further genomes are sequenced

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Assessing Patients with Alpha-1 Antitrypsin Deficiency for Corneal Refractive Surgery: A Review and Clinical Experience

Alpha-1 Antitrypsin Deficiency (AATD) is an autosomal inheritable disorder that impairs the protease inhibitor alpha-1 antitrypsin. This disorder presents with various systemic effects, including liver cirrhosis, centrilobular emphysema, and ocular manifestations. Performing corneal refractive surgery in patients with AATD raises concerns regarding the increased rates of corneal erosions, corneal ulcerations, potential developing descemetoceles, and other ocular manifestations. Patient outcomes for laser-assisted in situ keratomileuses (LASIK), photorefractive keratectomy (PRK), small incision lenticule extraction (SMILE), and other ocular corrective surgeries are lacking in this population. This article provides experiences performing corneal refractive surgery, discusses the current understanding of AATD, including its ocular manifestations, and explores factors to consider when evaluating patients for corneal procedures. The aim of this paper is to address the manifestations of AATD prior to performing corrective vision surgery

Herpes endotheliitis following laser-assisted in situ keratomileusis and photorefractive keratectomy

Herpes endotheliitis is a less common manifestation of herpes keratitis, and characteristic examination findings include corneal edema and the presence of keratic precipitates. Infection may be primary or secondary to herpes virus reactivation following exposure to a potential trigger such as physiologic stress or environmental factors. Ocular surgery, including laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK), can trigger reactivation in patients with or without a documented history of previous herpes infection. We present two patients with visually insignificant stromal scarring who denied a previous history of herpetic disease and developed herpes endotheliitis following LASIK and PRK. We demonstrate the importance of an appropriately thorough preoperative evaluation and further workup of any corneal abnormalities, even if such findings initially appear inconsequential

Antipsychotic Use in Pregnancy: Patient Mental Health Challenges, Teratogenicity, Pregnancy Complications, and Postnatal Risks

Pregnant women constitute a vulnerable population, with 25.3% of pregnant women classified as suffering from a psychiatric disorder. Since childbearing age typically aligns with the onset of mental health disorders, it is of utmost importance to consider the effects that antipsychotic drugs have on pregnant women and their developing fetus. However, the induction of pharmacological treatment during pregnancy may pose significant risks to the developing fetus. Antipsychotics are typically introduced when the nonpharmacologic approaches fail to produce desired effects or when the risks outweigh the benefits from continuing without treatment or the risks from exposing the fetus to medication. Early studies of pregnant women with schizophrenia showed an increase in perinatal malformations and deaths among their newborns. Similar to schizophrenia, women with bipolar disorder have an increased risk of relapse in antepartum and postpartum periods. It is known that antipsychotic medications can readily cross the placenta, and exposure to antipsychotic medication during pregnancy is associated with potential teratogenicity. Potential risks associated with antipsychotic use in pregnant women include congenital abnormalities, preterm birth, and metabolic disturbance, which could potentially lead to abnormal fetal growth. The complex decision-making process for treating psychosis in pregnant women must evaluate the risks and benefits of antipsychotic drugs

Antipsychotic Use in Pregnancy: Patient Mental Health Challenges, Teratogenicity, Pregnancy Complications, and Postnatal Risks

Pregnant women constitute a vulnerable population, with 25.3% of pregnant women classified as suffering from a psychiatric disorder. Since childbearing age typically aligns with the onset of mental health disorders, it is of utmost importance to consider the effects that antipsychotic drugs have on pregnant women and their developing fetus. However, the induction of pharmacological treatment during pregnancy may pose significant risks to the developing fetus. Antipsychotics are typically introduced when the nonpharmacologic approaches fail to produce desired effects or when the risks outweigh the benefits from continuing without treatment or the risks from exposing the fetus to medication. Early studies of pregnant women with schizophrenia showed an increase in perinatal malformations and deaths among their newborns. Similar to schizophrenia, women with bipolar disorder have an increased risk of relapse in antepartum and postpartum periods. It is known that antipsychotic medications can readily cross the placenta, and exposure to antipsychotic medication during pregnancy is associated with potential teratogenicity. Potential risks associated with antipsychotic use in pregnant women include congenital abnormalities, preterm birth, and metabolic disturbance, which could potentially lead to abnormal fetal growth. The complex decision-making process for treating psychosis in pregnant women must evaluate the risks and benefits of antipsychotic drugs