Deletion of Genes Implicated in Protecting the Integrity of Male Germ Cells Has Differential Effects on the Incidence of DNA Breaks and Germ Cell Loss

Infertility affects approximately 20% of couples in Europe and in 50% of cases the problem lies with the male partner. The impact of damaged DNA originating in the male germ line on infertility is poorly understood but may increase miscarriage. Mouse models allow us to investigate how deficiencies in DNA repair/damage response pathways impact on formation and function of male germ cells. We have investigated mice with deletions of ERCC1 (excision repair cross-complementing gene 1), MSH2 (MutS homolog 2, involved in mismatch repair pathway), and p53 (tumour suppressor gene implicated in elimination of germ cells with DNA damage).We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic) germ cells. Sertoli cell-only tubules were detected in testes from mice lacking expression of ERCC1 or MSH2 but not p53. The number of sperm recovered from epididymes was significantly reduced in mice lacking testicular ERCC1 and 40% of sperm contained DNA breaks whereas the numbers of sperm were not different to controls in adult Msh2 -/- or p53 -/- mice nor did they have significantly compromised DNA.These data have demonstrated that deletion of Ercc1, Msh2 and p53 can have differential but overlapping affects on germ cell function and sperm production. These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility

Neonatal and maternal postpartum bacteroides bacteremia

OBJECTIVE: A unique case of Bacteroides fragilis bacteremia in a mother and her infant prompted a review of these infections in neonates and postpartum mothers during a five-year period at two institutions in Winnipeg, Manitoba. The purpose was to determine the frequency of these infections and ascertain commonly associated factors. METHODS: Infants and postpartum mothers diagnosed with bacteroides bacteremia were identified from laboratory records in both hospitals, and their medical charts were retrospectively reviewed. RESULTS: Bacteroides species were isolated in 10 maternal and four neonatal blood cultures. This represented 8.1% of the positive maternal and 1.2% of the positive neonatal blood cultures obtained during the review. The incidence of maternal infection was 2.56/10,000 deliveries, while that of neonatal infection was 1.03/10,000 live births. Postpartum fever and emergency caesarean section were often noted with maternal postpartum bacteroides bacteremia, while fetal distress, low Apgar scores and respiratory distress were frequent in neonatal bacteremia. CONCLUSION: Postpartum bacteroides bacteremia should be suspected among women with postpartum fever after emergency caesarean section. However, the occurrence of postpartum fever following emergency caesarian section is not necessarily associated with neonatal bacteroides bacteremia. Neonatal bacteroides bacteremia may not be readily suspected on clinical grounds, so clinicians should ensure that the laboratory procedures routinely used to evaluate neonatal bacteremia at their institutions reliably detect these organisms. Key Words: Bacteroides; Bacteroides fragilis; Neonate; Postpartum bacteremia; Sepsis Bactériémie à bacteroides chez le nouveau-né et la mère en période postpartum OBJECTIF : Un cas unique de bactériémie à Bacteroides fragilis chez une mère et son bébé est à l'origine d'une revue de ces infections néonatales et maternelles en période postpartum pendant une période de cinq ans dans deux établisse-ments de Winnipeg, au Manitoba. L'objectif était de déterminer la fréquence de ces infections et d'établir les facteurs qui y sont généralement associés. MÉTHODES : Les bébés et les mères en période postpartum chez qui un diagnostic de bactériémie à bacteroides a été posé, ont été identifiés à partir des dossiers de laboratoire dans les deux établissements puis, les dossiers médicaux de ces patients ont été passés en revue de façon rétrospective. RÉSULTATS : Des espèces des bacteroides ont été isolées d'hémocultures de 10 mères et de quatre nouveau-nés. Ceci représentait 8,1 % d'hémocultures maternelles positives et 1,2 % d'hémocultures néonatales positives recueillies pendant l'étude. L'incidence d'infection maternelle était de 2,56/10 000 accouchements, alors que l'infection néonatale était de voir page suivante W hile Bacteroides fragilis bacteremia is often seen in women during the puerperal period, we have rarely observed it as a cause of neonatal sepsis (1-10). However, despite its clinical rarity, B fragilis was the third most common cause of neonatal bacteremia in one report, and the fourth most common isolate in another CASE PRESENTATION The mother was previously healthy, 22 years old, gravida 1, parida O and married. She presented in labour at 36 weeks' gestation following an uneventful pregnancy. Labour duration was 13.5 h, but 3 h before spontaneous vaginal delivery, the membranes were artificially ruptured, revealing thick meconium. The mother remained well until 36 h after delivery when she developed headache, malaise, fever of 38.9°C and signs of mild endometritis. Her peripheral blood count revealed a white blood cell count of 10,600/mm 3 with 75.6% mature neutrophils, a hemoglobin of 10.6 g/L, and a platelet count of 181,000/mm 3 . Urine culture was negative, but a blood culture grew B fragilis that was beta-lactamase-positive and sensitive to cefoxitin, pipercillin, clindamycin, chloramphenicol and metronidazole. Clindamycin and gentamicin had been started empirically but gentamicin was discontinued once the results of blood cultures were known. After three days of antibiotic therapy, the mother became afebrile and was discharged home three days later. The liveborn male infant weighed 2860 g with Apgar scores of five at 1 min and eight at 5 mins. Vital signs were temperature of 36.4°C, respiratory rate of 52 breaths/min and pulse of 125 beats/min. The infant was pale with hypotonia and moderate respiratory distress, and required intubation and artificial ventilation for 6 h. His white blood cell count was 19,800/mm 3 with 84.7% mature polymorphonuclear leukocytes and no immature forms. Hemoglobin was 15.1 g/L and the platelet count was 213,000/mm 3 . The lumbar puncture was grossly bloody with 873 white cells/mm 3 and no organisms were seen on Gram stain. Urinalysis was normal. Chest radiograph was consistent with mild respiratory distress syndrome. Urine, meconium and cerebral fluid cultures were sterile, but a blood culture grew B fragilis with an antibiotic susceptibility pattern identical to his mother's isolate. Antibiotics then were changed from empirical ampicillin and gentamicin to intravenous metronidazole. With this, the infant improved, and repeat blood cultures were sterile. Metronidazole was continued for 14 days. RETROSPECTIVE REVIEW Records of the Medical Microbiology Laboratories at the Health Sciences Centre and St Boniface Hospital, Winnipeg, Manitoba, were searched for bacteroides species recovered from blood cultures obtained from the neonatal units and the postpartum wards during the five-year period preceding this infant's birth. Prenatal status, labour and postpartum condition for each mother were evaluated, as well as the initial clinical status after birth, laboratory data and outcome of each neonate. From these wards, 5250 blood cultures were submitted during the five-year period. In both institutions, blood for neonatal blood cultures is usually obtained by using a single PediBacT Alert (Organon Teknika Corporation, North Carolina) bottle, which is routinely vented. Generally, blood for maternal blood cultures is obtained in both anaerobic and aerobic culture media bottles. All blood cultures are processed using the BacT Alert Automated Incubator (Organon Teknika Corporation). Four hundred and forty-two (8.4%) were positive for one or more organisms. Of these, 123 (27.8%) were from postpartum mothers and 319 (72.2%) were from neonates. Bacteroides species were isolated in 10 (8.1%) of 123 positive maternal cultures and in four (1.2%) of 319 positive neonatal cultures. This represents an incidence of 2.56 maternal infections/10,000 deliveries and 1.03 neonatal infections/10,000 live births. Details concerning the clinical factors reviewed Can J Infect Dis Vol 10 No 5 September/October 1999 359 Bacteroides bacteremia 1,03/10 000 naissances vivantes. La fièvre en postpartum et la pratique d'une césarienne d'urgence étaient souvent associées à une bactériémie à bactéroides chez la mère en postpartum, alors qu'une détresse foetale, des indices d'Apgar bas et une détresse respiratoire étaient fréquents dans les cas de bactériémie néonatale. CONCLUSION : On doit suspecter une bactériémie à bacteroides chez les femmes en postpartum accusant de la fièvre après avoir subi une césarienne d'urgence. Cependant, cette fièvre n'est pas obligatoirement associée à une bactériémie néonatale à bacteroides. La bactériémie néonatale à bacteroides peut ne pas facilement être décelée sur les seules bases cliniques, de sorte que les cliniciens devraient s'assurer que les techniques de laboratoire, utilisées de façon systéma-tique pour évaluer une bactériémie néonatale dans leurs établissements, dépistent ces organismes de façon fiable. from the 10 cases of maternal postpartum bacteroides bacteremia are described in DISCUSSION The true incidence of neonatal bacteroides bacteremia is difficult to ascertain because specific anaerobic blood cultures are not routinely performed in neonates. However, because empirical therapy of neonatal sepsis is not usually adequate for these organisms, a high index of suspicion can assist in earlier identification and institution of appropriate therapy to decrease the associated high morbidity and mortality. The purpose of this investigation was to ascertain the frequency of bacteroides bacteremia in our populations and the potential factors associated with them. Neonatal bacteroides bacteremia accounted for 1.2% of infant bacteremias and for 8.1% of bacteremias detected among postpartum women. This frequency of neonatal bacteroides bacteremia is similar to previous reports (1.1% to 17%) despite the changes in nomenclature of this group of organisms that have occurred since they were published (14-16). However, the incidence of neonatal B fragilis bacteremia was only 1.03 infections/10,000 live births, considerably lower than the 1.17 cases/1,000 live births reported by Chow et al (13) in 1974, which is the only other reported incidence data. This may reflect differences in the patient populations studied, obstetrical care practices or the blood culture techniques used. There are no comparable maternal statistics. Our index case is the only reported instance in which both the mother and infant were bacteremic with this organism. We did not detect any other case in the English literature indexed in MEDLINE and after reviewing the published papers cited in this report. That this is a rare event may reflect different risk factors predisposing postpartum and neonatal infections. Nine (90%) of 10 mothers with bacteroides species bacteremia had postpartum fever (temperature 38.5°C or greater) and six (60%) had caesarean section deliveries, which is consistent with previous reports (3,17). Our neonatal patients with bacteroides bacteremia tended to be premature, had respiratory distress at birth if liveborn, and had Apgar scores at 1 min of age. Only the index pregnancy was complicated with postpartum endometritis, and that followed a vaginal, not a caesarean section, delivery. Also, only one pregnancy was complicated with prolonged rupture of placental membranes. Chow et al In summary, we have presented an unusual instance in which both a mother and her newborn infant became bacteremic with B fragilis, and have shown that the diagnosis of this infection during the neonatal period is uncommon. We have also added four more cases to the neonatal literature that help confirm that fetal distress, respiratory distress and low Apgar scores at 1 min of age are factors associated with bacteroides infections in the neonate

Throat colonization of neonatal nursery staff by Ureaplasma urealyticum: An infection control or occupational health consideration?

Very low birth weight infants often have protracted respiratory tract colonization with Ureaplasma urealyticum. To determine whether prolonged contact with very low birth weight infants resulted in higher rates of upper respiratory tract colonization with this organism for caregivers, throat swabs for U urealyticum culture were obtained from medical, nursing and other support staff working in the neonatal intensive care and level II nurseries at the Health Sciences Centre and the St Boniface Hospital in Winnipeg, Manitoba. Throat colonization by U urealyticum was demonstrated in 7.3% (95% ci 0 to 15.6%) of 41 nurses working in the intensive care nurseries but in none of the 48 nurses working in other locations or the 66 other individuals tested (P=0.02). However, throat colonization was not significantly higher among the neonatal intensive care nurses than among the women delivering at one of the study institutions. Close contact with very low birth weight infants appears to constitute a minimal risk for increased throat colonization with U urealyticum among hospital staff members

Mother-To-Child Transmission Of Human Immunodeficiency Virus Type 1: Report From The Nairobi Study

Mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) is a significant problem in countries with endemic HIV-1 infection. Between 1986 and 1991, 365 children of HIV-L-infected mothers and 363 control children were studied in Kenya. The overall risk of transmission from mother to child, determined by serologic evidence of infection by age ⩽5? 12 months and excess mortality in the HIV-I-exposed group, was 42.8% (range, 27.6%-62.2%). Marriage was the only maternal characteristic associated with transmission (odds ratio, 2.2; 95% confidence interval, 1.2–4.2; P \u3c .05). Children who experienced growth failure were more likely to be infected. In 44% of children ultimately infected, the pattern of antibody response implied intrapartum or postnatal exposure to HIV-1. Of potential postnatal exposures examined, duration of breast-feeding beyond age 15 months and the mother being married were independently associated with increased risk of infection and seroconversion of children. The percentage of HIV infection attributable to breast-feeding ⩽5? 15 months was 32%. The frequency of mother-to-child transmission of HIV-I was high; a substantial proportion of infection occurred postnatally, possibly through breast-feeding

A Study of the Infant Nasal Microbiome Development over the First Year of Life and in Relation to Their Primary Adult Caregivers Using <i>cpn60</i> Universal Target (UT) as a Phylogenetic Marker

<div><p>Whereas the infant gut microbiome is the subject of intense study, relatively little is known regarding the nares microbiome in newborns and during early life. This study aimed to survey the typical composition and diversity of human anterior nare microflora for developing infants over time, and to explore how these correlate to their primary caregivers. Single nare swabs were collected at five time points over a one-year period for each subject from infant-caregiver pairs. Our study comprised of 50 infants (recruited at 2 weeks, post delivery) and their 50 primary caregivers. Applying the chaperonin-60 (<i>cpn60)</i> universal target (UT) amplicon as our molecular barcoding marker to census survey the microbial communities, we longitudinally surveyed infant nares microbiota at 5 time points over the course of the first year of life. The inter- and intra-subject diversity was catalogued and compared, both longitudinally and relative to their adult primary caregivers. Although within-subject variability over time and inter-subject variability were both observed, the assessment detected only one or two predominant genera for individual infant samples, belonging mainly to phyla Actinobacteria, Firmicutes, and Proteobacteria. Consistent with previously observed microbial population dynamics in other body sites, the diversity of nares microflora increased over the first year of life and infants showed differential operational taxonomic units (OTUs) relative to their matched primary caregiver. The collected evidence also support that both temporal and seasonal changes occur with respect to carriage of potentially pathogenic bacteria (PPBs), which may influence host predisposition to infection. This pilot study surveying paired infant/caregiver nare microbiomes provides novel longitudinal diversity information that is pertinent to better understanding nare microbiome development in infants.</p></div

Richness and Diversity of Nares Microbiota in Infants and their Primary Caregivers.

<p>Richness and Diversity of Nares Microbiota in Infants and their Primary Caregivers.</p

A Study of the Infant Nasal Microbiome Development over the First Year of Life and in Relation to Their Primary Adult Caregivers Using <i>cpn60</i> Universal Target (UT) as a Phylogenetic Marker - Fig 1

<p><b>Average relative abundance of phyla (A) and genera (B) in the nares microbiota of infants and their associated primary caregivers across five time points during the first year of life.</b> Relative abundance depicted represents the average values derived from each subject grouping at each sampling time point T1-T5 (range: 22–35 subjects per time point, in a possible maximum <i>n</i> = 40 study subject pairs).</p

Characteristics of children admitted to hospital with acute SARS-CoV-2 infection in Canada in 2020

Background: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease. Methods: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital. Results: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19. Interpretation: Among children who were admitted to hospital with SARSCoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche