Uropathogenic Escherichia coli (UPEC)-associated epididymitis is commonly diagnosed in outpatient settings. Although the infection can be successfully cleared using antimicrobial medications, 40% of patients unexplainably show persistent impaired semen parameters even after treatment. Our aim was to investigate whether pathogenic UPEC and its associated virulence factor hemolysin (hlyA) perturb the structural and functional integrity of both the epididymis and sperm, actions that may be responsible for the observed impairment and possibly a reduction of fertilization capabilities. Semen collected from patients diagnosed with E. coli-only related epididymitis showed that sperm counts were low 14 days postantimicrobial treatment regardless of hlyA status. At Day 84 following treatment, hlyA production correlated with approximately 4-fold lower sperm concentrations than in men with hlyA-negative strains. In vivo experiments with the hlyA-producing UPEC CFT073 strain in a murine epididymitis model showed that just 3 days postinfection, structural damage to the epididymis (epithelial damage, leukocyte infiltration, and edema formation) was present. This was more severe in UPEC CFT073 compared to nonpathogenic E. coli (NPEC 470) infection. Moreover, pathogenic UPEC strains prematurely activated the acrosome in vivo and in vitro. Raman microspectroscopy revealed that UPEC CFT073 undermined sperm integrity by inducing nuclear DNA damage. Consistent with these observations, the in vitro fertilization capability of hlyA-treated mouse sperm was completely abolished, although sperm were motile. These findings provide new insights into understanding the possible processes underlying clinical manifestations of acute epididymitis.
Adolescents with disabilities have great difficulty with academic content in middle school, and their teachers have difficulty teaching them to understand and use academic language. We taught teachers of sixth-grade students with learning disabilities, more than half of whom were also English language learners (ELLs), to implement about 15 min of daily interactive vocabulary instruction in their intact special education English/language arts classes. Three schools were assigned randomly to treatment (two schools) or control conditions (one school, 52 students total). We developed instructional routines to introduce four new words per week in three 4-week units to test for replicability. ANCOVAs (with each cycle’s pretest and intelligence quotient as covariates) were conducted on taught vocabulary, all of which favored the treatment condition with effect sizes ranging .6 to .7 per cycle. Near-transfer effects to vocabulary usage were weaker, with significant effects in the last two cycles. Effects were similar for students with disabilities who were ELLs and native English speakers. Treated students maintained their knowledge of words 4 to 24 weeks following the close of treatment.
This four-year longitudinal research was designed to study special education determinations of students who participated in Tier 2 intervention in a Response to Intervention (RtI) model focused on reading across Grades 1 through 4. We compared identification rates for learning disabilities and student characteristics of 381 students the year prior to implementation with 377 students in the RtI environment. Across schools 38 to 60% of students were English Language Learners (ELL). Key outcomes by Grade 4 for students with learning disabilities who had participated in a model of RtI were relatively greater reading impairment with effect sizes ranging from 0.64 to 0.82, and more equitable representation across ELL and native English speakers than in the cohort prior to RtI implementation. Notably, one-third of the students identified for special services as LD in these schools were not identified until 4 th grade.
We tested the effects of teaching reading skills through U.S. history content for 38 eighth-grade poor readers whose reading ability ranged from second- to fourth-grade levels. Half of the students received special education services, and half of the students were English language learners. Students were taught to decode multisyllabic words, learn meanings of academic words, and identify cause-and-effect relationships. They used easy levels of history text and then bridged into more difficult text accounts of the same events. Results showed gains in performance across each cycle in each reading component. Comparisons between students in the intervention and their typically developing peers showed stronger gains for intervention students in vocabulary and comprehension strategies. Students with disabilities who received instruction in causes and effects of historical events scored similarly to typical readers in their general education history classes.
At present, evaluation of male reproductive function consists primarily of routine semen analysis, a collection of conventional microscopic assessments ideally performed following the guidelines set by the World Health Organization. While providing some insight into testicular function, these long-performed tests are limited in the information that they impart; more specifically, they are unable to predict true fertility potential. As a consequence, there is a need for the appraisal and consideration of newer semen parameters that may be more indicative of reproductive success. Although various novel assays have been introduced that broaden the scope of information available to both researcher and clinician, the utility of these tests remains limited due to the lack of standardisation of protocols and the absence of clinically established, dependable reference ranges. As such, it is not surprising that most of these parameters and their associated methods remain recommended for 'research purposes only'. With the burgeoning 'omics' revolution, nanotechnology and the development of new analytical instruments, there is now an opportunity for the identification and measurement of previously unknown features that may prove to be more indicative of each sperm's true functional status and capability. Once optimised, simplified, clinically validated and made more readily accessible, these new approaches hold the promise of forming the fulcrum upon which andrological investigations can enter a new era.
BACKGROUND The last 20 years have seen an enormous upsurge in the number of publications reporting findings obtained by Raman spectroscopy, a non-invasive, non-destructive method which uses the inelastic scattering of light to provide a 'fingerprint' of the sample's chemical composition and constituents. Long neglected because of practical difficulties, the technique has been transformed by recent technological advances into a powerful analytical tool capable of opening avenues of investigation that were previously out of the reach of biomedical scientists. Beyond introducing the approach and describing its relative merits and weaknesses, the aim of this review is to provide a spur for discussion of what may become an invaluable tool for biomedical investigations. METHODS A comprehensive review of the literature was conducted searching PubMed and Ovid databases using numerous MeSH terms associated with reproductive medicine. Furthermore, the reference lists of all reported literature were explored. The searches were restricted to English language articles published in the last 50 years. RESULTS Beginning with simple characterizations of biologically and medically important substances, aided by increasing technological sophistication, the use of Raman spectroscopy in biomedicine has quickly expanded to the investigation of complex biochemical interactions, the assessment of organelles and now the evaluation of living cells and tissue. The first Raman investigations of reproductive organs were primarily oncological in nature; however, the past few years have seen an increase in the application of the technique for the assessment and evaluation of both male and female gametes. In particular, progress has been made in the characterization, identification and localization of sperm nuclear DNA damage. CONCLUSIONS The use of Raman spectroscopy has already provided many tantalizing glimpses into the potential that the technique has to answer many of the unresolved issues in investigative and therapeutic reproductive medicine. However, without stringent assessment and the clear representation of the methods' findings, their true meaning cannot be revealed nor should any conclusions be hastily derived. For the potential of Raman microspectroscopy to be truly realized, the dependability and reliability of the technique and its results can only be ascertained by multidisciplinary collaborations that undertake carefully conducted, controlled and analysed studies.
Helping struggling readers to learn history content in middle school can be difficult due to heavy reading demands. In this study, researchers taught poor readers with and without disabilities in eighth grade to generate main idea statements; create, compare, and contrast paragraphs; and identify cause and effect relations, along with relevant multisyllabic word study and vocabulary, as they read history text. The 34 participating students included 14 with disabilities and 20 without disabilities, who scored below the 5th percentile in reading, on average. The results were compared across special education and English learner status and with 81 typical readers from the same classes who studied the same units of history. Treated students made significant gains in use of these strategies, and poor readers with and without disabilities performed similar to their typical reader classmates in two of the three strategies following instruction. The instructional routines for each strategy are described.
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