Higher Abnormal Rate Research Articles

High Rates of Overuse-Related Structural Abnormalities in the Lumbar Spine of Youth Competitive Alpine Skiers: A Cross-sectional MRI Study in 108 Athletes.

Background:Alpine ski racing is known as a sport with unfavorable spinal loads and high rates of back overuse injuries at the elite level. However, little is known about overuse-related structural abnormalities occurring in the spine of youth athletes.Purpose:To describe the prevalence of abnormal magnetic resonance imaging (MRI) findings in the lumbar spine of youth competitive alpine skiers within the U16 category (under 16 years) with respect to sex, height growth, multifidus size, increasing age, and clinical relevance.Study Design:Cross-sectional study; Level of evidence, 3.Methods:A total of 108 youth competitive alpine skiers aged 13 to 15 years underwent MRI examination of the lumbar spine and measurement of the multifidus cross-sectional area on a 3-T Magnetom Prisma scanner. Complementary assessments included the determination of anthropometrics and biological maturation. Athletes were classified as symptomatic when, pursuant to the Oslo Sports Trauma Research Center questionnaire on health problems, at least 1 substantial back overuse–related health problem episode had been registered during the 12 months before the MRI examination.Results:Of the analyzed youth skiers, 37.0% presented with ≥1 abnormal MRI finding in the lumbar spine. The most prevalent findings in both sexes were disc degeneration (23.1%), Schmorl nodes (19.4%), end plate changes (10.2%), and pars interarticularis anomalies (10.2%); the pars interarticularis anomalies occurred exclusively in males. A smaller relative lumbar multifidus cross-sectional area was related to more frequent occurrence of disc protrusions (P = .018; R2 = 0.116) and end plate changes (P = .024; R2 = 0.096). Overall, the occurrence of abnormal MRI findings in the lumbar spine increased with age (P = .034; R2 = 0.054). Disc degeneration (particularly disc dehydration and disc protrusion) were significantly more prevalent in symptomatic versus asymptomatic athletes (P < .05 for all).Conclusion:As early as age 15 years or younger, competitive alpine skiers demonstrated distinct overuse-related structural abnormalities in the lumbar spine, with some of them being clinically relevant and restrictive of sports participation. As sex, height growth, multifidus size, and increasing age seem to play an important role for the occurrence of such abnormalities, considering these factors might be essential for prevention.

Autologous bone marrow mesenchymal stromal cell therapy for “no-option” critical limb ischemia is limited by karyotype abnormalities

BackgroundCritical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%–40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need. Mesenchymal stromal cells (MSCs) may provide salvage therapy through their angiogenic and tissue-trophic properties. This article reports a phase 1b clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI. MethodsTwelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs. ResultsA high rate of karyotype abnormality (>30%) was detected in the produced cell batches, resulting in failure of release for clinical administration. Four patients were treated with the investigational medicinal product (IMP), three with a low dose of 20 × 106 MSCs and one with a mid-dose of 40 × 106 MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy. ConclusionsThe results of this trial conclude that an autologous cell therapy approach with MSCs for critical limb ischemia is limited by the high rate of karyotype abnormalities.

Targeting replication stress response using polypurine reverse hoogsteen hairpins directed against WEE1 and CHK1 genes in human cancer cells

In response to DNA damage, cell cycle checkpoints produce cell cycle arrest to repair and maintain genomic integrity. Due to the high rates of replication and genetic abnormalities, cancer cells are dependent on replication stress response (RSR) and inhibitors of this pathway are being studied as an anticancer approach. In this direction, we investigated the inhibition of CHK1 and WEE1, key components of RSR, using Polypurine Reverse Hoogsteen hairpins (PPRHs) as gene silencing tool. PPRHs designed against WEE1 or CHK1 reduced the viability of different cancer cell lines and showed an increase of apoptosis in HeLa cells. The effect of the PPRHs on cell viability were dose- and time-dependent in HeLa cells. Both the levels of mRNA and protein for each gene were decreased after treatment with the PPRHs. When analyzing the levels of the two CHK1 mRNA splicing variants, CHK1 and CHK1-S, there was a proportional decrease of the two forms, thus maintaining the same expression ratio. PPRHs targeting WEE1 and CHK1 also proved to disrupt cell cycle after 15 h of treatment. Moreover, PPRHs showed a synergy effect when combined with DNA damaging agents, such as methotrexate or 5-Fluorouracil, widely used in clinical practice. This work validates in vitro the usage of PPRHs as a silencing tool against the RSR genes WEE1 and CHK1 and corroborates the potential of inhibiting these targets as a single agent therapy or in combination with other chemotherapy agents in cancer research.

&lt;p&gt;The Occurrence and Longitudinal Changes of Cognitive Impairment After Acute Ischemic Stroke&lt;/p&gt;

Background and PurposeMore and more evidence suggests that cognitive impairment (CI) after stroke is closely related to the quality of life of stroke patients. The primary aim of this study is to investigate the occurrence and longitudinal changes of CI at different stages after acute ischemic stroke (AIS) in Chinese patients.MethodsThe data of this study come from the impairment of cognition and Sleep after acute ischemic stroke or transient ischemic attack in Chinese patients study (ICONS), a nationwide multicenter prospective registry that recruited consecutive AIS or transient ischemic attack in-hospital patients within 7 days after onset. Patients were followed for Montreal Cognitive Assessment (MoCA) scale at 2-week (2w), 3 months (3m) and 12 months (12m). CI was defined as MoCA score≦22. No cognitive impairment (NCI) was defined as MoCA score>22.ResultsA total of 2432 AIS patients were enrolled in this study. Overall, 72.94% of patients were male and the average age was 60.95 years. Median National Institutes of Health Stroke Scale score was 3. The occurrence rate of CI was 52.38%, 35.55% and 34.16% at 2w, 3m and 12m. Among patients with CI at 2w and 3m, 39.9% and 27.9% of patients returned to NCI at next follow-up point. At 3m and 12m follow-up, there were also 9.6% and 12.7% new CI patients. The two cognitive items with the highest abnormal rate were “Delayed recall” (89.35%, 83.33% and 82.80%) and “Visuospatial/executive” (78.91%, 73.42% and 70.08%). The cognitive item with the highest percentage of improved patients was “Orientation” (60.91–76.68%), and the cognitive item with the lowest percentage of improved patients was “Language” (35.85–44.50%).ConclusionCI had a relatively high occurrence at 2w to 12m after AIS. CI at 3m and 12m was significantly lower than that at 2w after stroke. The occurrence of abnormalities and recovery probability for different cognitive items also differed greatly.

Genetic diagnosis and sperm retrieval outcomes for Chinese patients with congenital bilateral absence of vas deferens.

Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of obstructive azoospermia. CBAVD is mainly caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene and is also related to the X-linked ADGRG2 (adhesion G protein-coupled receptor G2) gene. Genetic screening and counseling strategies for Chinese CBAVD populations remain controversial because the genetic background of CBAVD in Chinese population is largely unknown. In this study, we aimed to study the mutation spectrum of CFTR and ADGRG2 in a group of CBAVD patients and to evaluate sperm retrieval outcomes in a subset of CBAVD patients. Next-generation targeted sequencing was used to identify mutations in the CFTR and ADGRG2 genes in 38 CBAVD patients. In addition, we followed and analyzed nine of the 38 patients who were undergoing sperm retrieval surgery. In total, 27 of 38 (71.05%) patients carried at least one likely pathogenic or pathogenic mutation in CFTR or ADGRG2. In addition to the IVS9-5T allele, 15 CFTR and 1 ADGRG2 mutations were identified, including 4 novel mutations. CFTR hot-spot mutations were not identified in our study. Spermatozoon was successfully obtained in all nine patients who underwent MESA or TESE surgery, but most patients had spermatozoa with relatively low motility and high abnormality rates. Except for the IVS9-5T allele, hot-spot mutations of CFTR may not exist in Chinese CBAVD patients. Therefore, next-generation targeted sequencing for whole CFTR and ADGRG2 gene may be the appropriate genetic testing method, and genetic counseling may be different from Caucasian populations. We observed a high success rate of sperm retrieval with relatively low motility and high abnormality rates in Chinese CBAVD patients. However, this is only a weak conclusion due to the small sample size.

Environmental and Hygienic Assessment of Ambient Air Pollution in Oil-Producing and Oil-Refining Areas of the Republic of Bashkortostan and Population Health Status

Introduction. High density of oil-producing and refining facilities in certain areas of Bashkortostan significantly affects the environment including ambient air quality in residential areas. Materials and methods. We analyzed concentrations of airborne toxicants (sulfur and nitrogen oxides, nitrogen and carbon oxides, hydrogen sulfide, ammonia, xylenes, toluene, phenol and total suspended particles) and population health status in the cities of Ufa, Sterlitamak, Salavat, Blagoveshchensk, and the Tuymazinsky District in 2007–2016. Pearson's correlation coefficients (r) were used to establish possible relationships between medico-demographic indicators and air pollution. Results. Republican fuel and energy enterprises contributed the most to local air pollution levels. Gross emissions from such enterprises as Bashneft-Ufaneftekhim and Bashneft-Navoil reached 43.69–49.77 thousand tons of pollutants per year. The levels of some air pollutants exceeded their maximum permissible concentrations. Elevated concentrations of ammonia, total suspended particles, nitrogen dioxide, and carbon monoxide were registered most frequently. High rates of congenital abnormalities, respiratory diseases in infants (aged 0-1), general mortality and morbidity of the population were observed in some oil-producing and refining areas. The correlation analysis proved the relationship between the concentration of carbon monoxide and general disease rates in adults based on hospital admissions (r = 0.898), general incidence rates in children (r = 0.957), and blood disease rates in infants (r = 0.821). Respiratory diseases in children correlated with nitrogen dioxide emission levels (r = 0.899). Conclusions. Further development of oil-producing, petrochemical and oil-refining industries should be carried out taking into account socio-economic living conditions of the population.

A Retrospective Review of Referral Rates for Genetic Screening of AYA Patients Diagnosed with Myeloid Malignancies and Aplastic Anemia

Introduction Genetic abnormalities can predispose patients to develop acute myeloid leukemia (AML), aplastic anemia (AA) and myelodysplastic syndrome (MDS). These mutations are more often seen in pediatric patients so genetic screening is more routinely performed in that population. Recent algorithms propose screening in adolescent and young adults (AYAs) with AML/AA/MDS. However, this is not routine practice in community hospitals where most AYAs are treated. Discovery of familial genetic abnormalities can impact donor choice in patients undergoing allogeneic stem cell transplant and treatment/screening in family members. Objectives The goal of this study is to determine the rate of genetic screening in AYAs with AML/AA/MDS based on recently proposed screening algorithms in a community hospital setting. Methods Patients with AML/AA/MDS aged ≤50 years treated at Prisma Health Upstate (2015 to 2019) were included in this retrospective study. While the AYA population is typically defined as ages 18-39, we included patients up to age 50 given screening recommendations from some centers. Charts were reviewed to determine rates of genetic screening based on published algorithms from M.D. Anderson Cancer Center. We compared rates of screening in pediatric and AYA patients and documentation of pertinent family history. Results Thirty-nine patients (12 pediatric, median age: 9 years; 27 AYA, median age: 33 years) diagnosed with AML (n=19)/MDS (n=6)/AA (n=14) were included in the study. Genetic screening was performed in 8/12 (67%) pediatric patients and 8/27 (30%) in AYAs (P Conclusions Screening for hereditary predispositions to hematologic malignancies in AYAs is underperformed despite recent evidence suggesting otherwise. We report low rates of screening in our community hospital where transplant is a treatment option for AYAs with MDS/AA/AML. In addition to donor considerations, predisposition syndromes can affect treatment toxicities, conditioning regimens, and screening of family members. Our results, despite the small sample size, indicate a high detection rate of genetic abnormalities and need for improving focused family history documentation. Based on our findings, we will implement an institution wide genetic screening protocol for AYAs with MDS/AA/AML.

Cytogenetic assessment of Iranian infertile men with undescended testis: A retrospective study.

Objective:Undescended testis (UDT) is a urogenital disease that affects fertility. This study looked into the cytogenetic abnormalities of Iranian infertile patients with UDT.Methods:Our study included 522 infertile patients with UDT (case group) and two control groups, one with 300 infertile men without UDT and another with 268 fertile men.Results:Chromosomal abnormalities were found in 45 patients with UDT (8.62%). Seven of the alterations were considered as normal features. Klinefelter syndrome and mosaicism were the most common anomalies. Chromosomal abnormalities were found in 31 infertile men in the control group (10.33%), 13 of which deemed normal and 18 (6%) anomalous. Nine chromosomal abnormalities were found in the second control group with fertile men (3.35%), six deemed normal and three (1.11%) anomalous.Conclusion: Despite the high rate of abnormalities in infertile controls (6%) and the higher rate seen in infertile individuals with UDT indicate a significant prevalence of chromosomal abnormalities in the Iranian population, particularly when the literature suggests that the normal rate of abnormal karyotypes should be within the 0.7-1% range in the general population. The incidence of abnormal karyotypes increased when infertile patients had additional conditions such as UDT.

Targeting transgene to seed resulted in high rate of morphological abnormalities of Camelina transformants

Abstract False flax (Camelina sativa L.) is currently under-exploited but highly promising oilseed crop. Combining Camelina’s attractive agronomic traits with its unprecedented ease for genetic engineering makes it an ideal plant chassis for biotechnology applications, in particular synthetic biology strategies. For targeted expression of transgene particularly to seeds requires identification and application of seed specific promoters. In the present study two cultivars of Camelina, namely Zuzana and Smilowska, were used for transformation at early flowering stage using the floral dip method. The plants were inoculated with Agrobacterium bearing a construct for expression of red fluorescent protein (RFP) under the control of the seed specific cruciferin promoter CRUC from Arabidopsis. Transgenic seeds and plants were identified on the basis of red fluorescence (RFP) and kanamycin resistance. Relatively high transformation efficiency of 8 % was achieved particularly for the cultivar Zuzana. However, many of regenerants exerted developmental deformations such as lack of shoot apical meristem, deformed or absent cotyledons, etc. Furthermore, the activity of the CRUC promoter was still active also in true leaves rendering this promoter as inappropriate for seed targeting of the transgene. Nevertheless, genetic transformation remains a tool for direct modulation of pathways for oil synthesis in oilseed crops.

The Asthenozoospermia as a Major Sperm Abnormality in Males Assessed for Semen Analysis in Institut Pasteur of Cote d’Ivoire

Objectives: The male infertility is on the increase worldwide; therefore, it is attracting more attention in several studies in order to improve its treatment management. The current study aimed at contributing to set up epidemiological and biological data and draw a general profile of male infertility in Cote d’Ivoire.Materials & Methods: The current prospective and descriptive study was conducted on 401 males` sperm obtained through masturbation after three days of abstinence. The analysis of the information in the cards accompanying the samples and the spermogram and spermocytogram analyses were used to collect the related data.Results: The average age of the males in the study was 39.97 years and the average duration of infertility was 6.66 years; 35.16% of the subjects were in the private sector and mostly composed of traders. Primary infertility was the leading cause of consultation in 55.61% of the cases. A significant relationship (P=0.03) between stress and azoospermia was highlighted, showing that males with stress were twice as likely to develop azoospermia (Odds Ratio=2.24). Results of the current study showed that in the vast majority, semen had several abnormalities with a high rate of associated abnormalities, 37.41%. However, among the isolated abnormalities, asthenozoospermia was the most prominent abnormality with a rate of 20.70%.Conclusion: This study shows that the sperms evaluated have many abnormalities, the most important of which is asthenozoospermia.

Screening and analysis of the serum thyroid stimulating hormone (TSH) of rural pregestational women In Yunnan province

Objective Through screening the serum TSH in rural pregestational women, fo find out the high incidence area and high risk population of thyroid disease in Yunnan province, to reduce the probability of infertility and abnormal pregnancy and provide important reference basis for prenatal aristogenesis. Methods The serum TSH level of 30 163 rural pregestational women(20-49 yeas old) which from 16 different areas and 16 different ethnicities of Yunnan province was detected by using TSH3-Ultra (TSH3-UL) reagent on a Siemens centar-XP automatic chemiluminescence apparatus. Results 1 797 women were found with abnormal serum TSH level, the abnormal rate was 5.96%. Among them, the proportion of women with decreased TSH was 3.09% and increased TSH was 2.87%, compared with the normal reference range. And there was a significant difference of abnormal serum TSH rate between pregestational women from different areas and ethnicities. Moreover, in the 16 tested areas, the highest abnormal serum TSH rate was 8.90% from Ximeng county, the lowest was 3.60% from Diqing state. However in the 16 tested ethnicities, the highest abnormal serum TSH rate was 9.73% from Lisu ethnic minority and the lowest was 3.60% from Tibetan ethnic minority. Conclusions The results inferred that ethnic and regional factors both to some extent affect the prevalence of thyroid disease in pregestational women and it is a small probability event that high occurrence of TSH decreased or increased situation simultaneously happened in one area or one ethnicity. Key words: Thyroid stimulating hormone; Pregestational Women; Rural areas; Minority of Yunnan Province

2561 Should Placental Abnormality be Expected in Subsequent Pregnancy after Myomectomy?

Study Objective To compare the incidence of placental abnormalities in subsequent pregnancy after myomectomy performed by laparoscopy, laparotomy and hysteroscopy. Design A retrospective cohort study, conducted from February 2011 to November 2018. Setting A single tertiary care center. Patients or Participants All women after myomectomy that gave birth. Interventions Data was collected from patients' medical files. Groups were compared for women demographics, fibroids characteristics, operative management, post-operative placental evaluation and delivery characteristics. Primary outcome was defined as the need for any intervention for placental separation during the third phase of the delivery. Non-parametric statistics were used for analysis. Measurements and Main Results 241 women met inclusion criteria. Complete follow-up was achieved in 199 (82.57%) women, of them 82, 89 and 28 underwent laparoscopic, laparotomy and hysteroscopic myomectomy, respectively. There were no significant differences between the groups in women's age, BMI, gravidity and history of cesarean deliveries. Endometrial damage during laparoscopy and laparotomy was reported in 3 (3.6%) and 7 (7.8%) of the women, respectively (p=0.21), and in all women undergoing hysteroscopic myomectomy (p=0.001). During subsequent pregnancy, morbidly adherent placenta was suspected in only one woman in each of the groups (p=0.63), a rate that is considered lower than the reported rate after one cesarean delivery. Placenta previa was not seen in any of the women included in the study. Normal vaginal delivery was significantly higher in the hysteroscopy group compared to laparoscopy and laparotomy groups [11 (36.3%) vs. 5 (6.1%) vs. 4 (4.5%); p=0.001], with significantly lower need for manual lysis of the placenta [11(39.0%) vs. 51 (62.1%) vs. 62 (69.7%); p=0.01] and no need for any further interventions to control blood loss. Conclusion Subsequent pregnancy after myomectomy was not found to be associated with high placental abnormality rate. Furthermore, other than manual lysis, no difference in abnormal placentation requiring intervention was seen between the different techniques.

Tolerance of High Oral Doses of Nonradioactive and Radioactive Caesium Chloride in the Pale Grass Blue Butterfly Zizeeria maha.

The biological effects of the Fukushima nuclear accident have been examined in the pale grass blue butterfly, Zizeeria maha (Lepidoptera: Lycaenidae). In previous internal exposure experiments, larvae were given field-collected contaminated host plant leaves that contained up to 43.5 kBq/kg (leaf) of radioactive caesium. Larvae ingested up to 480 kBq/kg (larva), resulting in high mortality and abnormality rates. However, these results need to be compared with the toxicological data of caesium. Here, we examined the toxicity of both nonradioactive and radioactive caesium chloride on the pale grass blue butterfly. Larvae were fed a caesium-containing artificial diet, ingesting up to 149 MBq/kg (larva) of radioactive caesium (137Cs) or a much higher amount of nonradioactive caesium. We examined the pupation rate, eclosion rate, survival rate up to the adult stage, and the forewing size. In contrast to previous internal exposure experiments using field-collected contaminated leaves, we could not detect any effect. We conclude that the butterfly is tolerant to ionising radiation from 137Cs in the range tested but is vulnerable to radioactive contamination in the field. These results suggest that the biological effects in the field may be mediated through ecological systems and cannot be estimated solely based on radiation doses.

Characteristics of first trimester miscarriages assesed by chromosomal analysis of products of conception with next generation sequencing

Chromosomal abnormalities are the major cause of early pregnancy loss. Chromosome testing of products of conception (POC) provides valuable information for counseling and clinical managing of patients. We previously showed that next generation sequencing (NGS) can be utilized as a technique demanding lesser specimen with a lower failure rate, higher resolution, and shorter turnaround time than conventional karyotyping which is requiring labor-intensive and time-consuming cell culture with possible maternal cell contamination. We aimed to assess the efficacy of NGS method for chromosomal analysis of POC. In addition, we attempted to identify any associations between the incidence of chromosomal abnormalities and the profile of patients as well as fetal development in an assisted reproductive technology (ART) program. Retrospective study with a single reference genetic laboratory. Total of 131 consenting patients with first trimester miscarriages after vitrified-warmed embryo transfer were involved. POC samples were obtained bydilation and curettage between 7 to 10 gestational weeks. Chorionic villi were isolated under a dissecting microscopy, subsequently processed for NGS chromosomal analysis. Incidence of each chromosomal abnormality was reported and evaluated according to the patient profile, such as maternal age, previous history of miscarriage and fetal development. Finally, frequency of mosaics was also assessed. After NGS analysis, 28 cases (21.4%) were found to be normal, and the remaining 103 (78.6%) were abnormal, including 10 (7.6%) mosaics. Among normal karyotypes, ratio of female to male was 1.15 (15/13). Trisomies were the most common abnormalities except for the chromosome X monosomy (10.7%). Aneuploidy of chromosome 22 (20/113, 17.7%), 15 (16/113, 14.2%), 16 (16/113, 14.2%), X (13/113, 11.5%) and 21 (11/113, 9.7%) including overlaps, were most frequently involved. Mean maternal age of chromosomally abnormal cases was significantly higher than that of normal karyotypes (39.0 ± 18.5 vs 36.9 ± 16.5 years, P<0.05). Patients with more than equal 3 previous miscarriages showed a significantly lower rate of abnormalities than those with <3 miscarriages (28.6% vs 81.5%, P<0.01). Rate of abnormalities with positive fetal cardiac activity was not different from that of anembryonic pregnancies (80.0% vs 76.1%), although fetal cardiac activity was detected in all the 45,XO cases. Interestingly, however, mosaic abnormalities were significantly more often detected in anembryonic pregnancies than the other (15.2% vs 3.5%, P<0.05). With more conclusive and accurate results and higher resolution by NGS, we were able to characterize early pregnancy loss after ART, demonstrating relatively high rate of abnormalities with gender ratio being close to 1. Patients with repeated pregnancy loss showed lower chromosomal abnormalities indicating other causes for miscarriages in this group of patients. A higher incidence of mosaics detected in anembryonic pregnancies warrants further investigation.

Pregnancy Outcomes in Women with Incidentally Detected Unicornuate Uteri.

To estimate the incidence of adverse pregnancy outcomes in women with incidentally detected unicornuate uteri. This is a descriptive study. Database review identified patients with unicornuate uteri and singleton pregnancies at ≥12 weeks' gestation. Patients were excluded if the diagnosis of unicornuate uterus was made after a midtrimester loss or preterm delivery. Records were reviewed to obtain clinical outcomes. Chi-square test, Fisher's exact test, and Mann-Whitney U-test were used for statistical analysis. Forty patients with 67 pregnancies were included. Most diagnoses were made during infertility work-up (76.2%). There was one midtrimester loss (1.5%). In the remaining 66 pregnancies, median gestational age at delivery was 38 weeks. There were 20 (30.3%) preterm births, 9 (13.6%) spontaneous preterm births, and 11 (16.7%) indicated preterm births. Women with indicated preterm births were more likely to have placental abnormalities. Of the available placental pathology, 45.2% had histological lesions of malperfusion. Cesarean delivery was performed in 77.3% of cases. Most women with incidentally detected unicornuate uteri gave birth at term. More than half the preterm births were indicated, with relatively high rates of placental abnormalities. In patients without a poor obstetrical history, rates of midtrimester loss and spontaneous preterm birth were lower than previously described.

Ophthalmologic Abnormalities in Children with Congenital Sensorineural Hearing Loss

ABSTRACTObjective: To review a single center experience with the diagnosis of visual impairment in patients with sensorineural hearing loss (SNHL) and propose a diagnostic algorithm.Study Design: Retrospective study of patients with SNHL who were diagnosed with ophthalmologic abnormalities in the course of evaluation.Setting: University children’s hospital and university-associated eye institute.Subjects and Methods: Children with the diagnosis of sensorineural hearing loss aged 0–18 who received a formal ophthalmology examination between the dates of December 2000-December 2016 were included for analysis. Children were identified using ICD-9 and ICD-10 billing codes. Primary measures included diagnosis of SNHL, ophthalmologic diagnoses, and referral source.Results: Two hundred and sixty-nine patients with SNHL met inclusion criteria. One hundred and thirty-one (48.5%) of these patients had an ophthalmic abnormality. When evaluating referral source, patients referred by a pediatrician following failed vision screen or visual complaint were more likely to have an ophthalmologic finding (61%, n = 147) when compared to referral by an otolaryngologist following diagnosis of SNHL (9.6%, n = 73). Seventeen of the 131 (13%) patients with at least one ophthalmic abnormality had an abnormality that was deemed unlikely to be detected by routine screening.Conclusion: Our study agreed with previously published works that there is a high rate of ophthalmic abnormalities in patients with SNHL. Evaluation of referral source for ophthalmology evaluation suggests that routine referral by otolaryngologists in patients with SNHL may not be an efficient means of identifying patients with treatable ophthalmic disease. Reliance on school and office screenings to detect ophthalmic abnormalities, prior to referral, is likely a more efficient model, even among patients with SNHL.

Toxicity evaluation of olive oil mill wastewater and its polar fraction using multiple whole-organism bioassays

Olive mill wastewater (OMW) as a by-product of olive oil extraction process has significant polluting properties mainly related to high organic load, increased COD/BOD ratio, high phenolic content and relatively acidic pH. Raw OMW from Slovenian Istria olive oil mill and its polar fraction were investigated in this study. Chemical characterization of OMW polar fraction identified tyrosol as the most abundant phenolic product, followed by catechol. Lethal and sub-lethal effects of OMW matrix and its polar fraction were tested using a battery of bioassays with model organisms: bacteria Vibrio fischeri, algae Chlorella vulgaris, water fleas Daphnia magna, zebrafish Danio rerio embryos, clover Trifolium repens and wheat Triticum aestivum. Raw OMW sample was the most toxic to V. fischeri (EC50 = 0.24% of OMW sample final concentration), followed by D. magna (EC50 = 1.43%), C. vulgaris (EC50 = 5.20%), D. rerio (EC50 = 7.05%), seeds T. repens (EC50 = 8.68%) and T. aestivum (EC50 = 11.58%). Similar toxicity trend was observed during exposure to OMW polar fraction, showing EC50 values 2.75–4.11 times lower comparing to raw OMW. Tested samples induced also sub-acute effects to clover and wheat (decreased roots, sprouts elongation); and to zebrafish embryos (increased mortality, higher abnormality rate, decreased hatching and pigmentation formation rate). A comprehensive approach using a battery of bioassays, like those used in this study should be applied during ecotoxicity monitoring of untreated and treated OMW.

A Low Critical Event Rate Despite a High Abnormal Event Rate in Patients with Cardiac Implantable Electric Devices Followed Up by Remote Monitoring.

Objective Remote monitoring (RM) of cardiac implantable electric devices (CIEDs) has been advocated as a healthcare standard. However, expert consensus statements suggest that all patients require annual face-to-face follow-up consultations at outpatient clinics even if RM reveals no episodes. The objective of this study was to determine the critical event rate after CIED implantation through RM. Methods This multicenter, retrospective, cohort study evaluated patients with pacemakers (PMs), implantable cardioverter defibrillators (ICDs), or cardiac resynchronization therapy defibrillator (CRT-Ds) and analyzed whether or not the data drawn from RM included abnormal or critical events. Patients A total of 1,849 CIED patients in 12 hospitals who were followed up by the RM center in Okayama University Hospital were included in this study. Results During the mean follow-up period of 774.9 days, 16,560 transmissions were analyzed, of which 11,040 (66.7%) were abnormal events and only 676 (4.1%) were critical events. The critical event rate in the PM group was significantly lower than that in the ICD or CRT-D groups (0.9% vs. 5.0% or 5.9%, p<0.001). A multivariate analysis revealed that ICD, CRT-D, and a low ejection fraction were independently associated with critical events. In patients with ICD, the independent risk factors for a critical event were old age, low ejection fraction, Brugada syndrome, dilated phase hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Conclusion Although abnormal events were observed in two-thirds of the transmitted RM data, the critical event rate was <1% in patients with a PM, which was lower in comparison to the rates in patients with ICDs or CRT-Ds. A low ejection fraction was an independent predictor of critical events.

Skin nerve pathology: Biomarkers of premanifest and manifest amyloid neuropathy.

Small-fiber sensory and autonomic symptoms are early presentations of familial amyloid polyneuropathy (FAP) with transthyretin (TTR) mutations. This study aimed to explore the potential of skin nerve pathologies as early and disease-progression biomarkers and their relationship with skin amyloid deposits. Skin biopsies were performed in patients and carriers to measure intraepidermal nerve fiber (IENF) density, sweat gland innervation index of structural protein gene product 9.5 (SGII[PGP9.5]) and peptidergic vasoactive intestinal peptide (SGII[VIP]), and cutaneous amyloid index. These skin pathologies were analyzed with clinical disability assessed by FAP stage score (stage 0-4) and compared to neurophysiological and psychophysical tests. There were 70 TTR-mutant subjects (22 carriers and 48 patients), and 66 cases were TTR-A97S. Skin nerve pathologies were distinct according to stage. In carriers, both skin denervation and peptidergic sudomotor denervation were evident: (1) IENF density was gradually reduced from stage 0 through 4, and (2) SGII(VIP) was markedly reduced from stage 1 to 2. In contrast, SGII(PGP9.5) was similar between carriers and controls, but it declined in patients from stage 2. Skin amyloids were absent in carriers and became detectable from stage 1. Cutaneous amyloid index was correlated with SGII(PGP9.5) and stage in a multivariate mixed-effect model. When all tests were compared, only IENF density, SGII(PGP9.5), and cutaneous amyloid index were correlated with stage, and IENF density had the highest abnormal rate in carriers. Biomarkers of sensory and sudomotor innervation exhibited a stage-dependent progression pattern, with sensory nerve degeneration as the early skin nerve pathology. Ann Neurol 2019;85:560-573.

Effectiveness of Surgical versus Conservative Treatment for Distal Femoral Growth Plate Fractures: A Systematic Review

Background and Objective:The objective of this review was to determine whether surgery, in comparison to conservative treatment, is a safe and effective intervention for the management of distal femoral growth plate fractures.Methods:A systematic literature review was performed using a three-step search strategy. The PubMed, Embase and Scopus databases were utilized to identify current studies from 1 January 1990 to 8 January 2017. Papers selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments. Primary outcomes of interest were rates of growth arrest and angular deformity.Results:Of the 7740 studies identified with the search, 15 case studies with data inclusive of outcomes of interest were selected for inclusion. A total of 466 patients were included.The rate of complication in the surgical population was 37.8%. In the conservative population the rate of complication was 34.0%. Five of the 15 papers showed Salter-Harris (SH) classification to correlate with prognosis, three papers showed the presence of displacement to correlate with prognosis which would have had an influence on the results of these higher graded injuries likely to have been managed operatively. A high rate of position loss and subsequent growth abnormalities was observed when conservative management was instituted.Conclusion:The rate of complication was marginally higher in the surgical population than that in the conservative population. This study also identified that higher severity distal femur physeal fractures, determined by the amount of displacement and Salter Harris grade, may associate a poorer outcome. It appears that managing higher severity distal femoral physeal injuries conservatively would be less likely to achieve and maintain reduction and therefore associate higher risks of malunion with subsequent growth arrest, leg length discrepancy and angular deformity as compared with surgical intervention. Further studies with higher patient numbers and comparable cohorts are needed to compare surgical and conservative interventions for the lower severity distal femoral physeal fractures.