Developmental stage and morphology of the competent blastocyst are associated with sex of the child but not with other obstetric outcomes: a multicenter cohort study.

STUDY QUESTION: Are transfer day, developmental stage and morphology of the competent blastocyst in pregnancies leading to live birth associated with preterm birth, birthweight, length at birth and sex of the child? SUMMARY ANSWER: A high score in blastocyst developmental stage and in trophectoderm (TE) showed a significant association with the sex of the child, while no other associations with obstetric outcomes were observed. WHAT IS KNOWN ALREADY: The association between blastocyst assessment scores and obstetric outcomes have been reported in small single-center studies and the results are conflicting. STUDY DESIGN, SIZE, DURATION: Multicenter historical cohort study based on exposure data (transfer day (blastocyst developmental stage reached by Day 5 or Day 6)) blastocyst developmental stage (1-6) and morphology (TE and inner cell mass (ICM): A, B, C)) and outcome data (preterm birth, birthweight, length at birth, and sex of the child) from women undergoing single blastocyst transfer resulting in a singleton pregnancy and live birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 16 private and university-based facilities for clinical services and research were used. A total of 7246 women, who in 2014-2018 underwent fresh-embryo transfer with a single blastocyst or frozen-thawed embryo transfer (FET) with a single blastocyst resulting in a singleton pregnancy were identified. Linking to the Danish Medical Birth Registry resulted in a total of 4842 women with a live birth being included. Cycles with pre-implantation genetic testing and donated gametes were excluded. The analyses were adjusted for female age (n = 4842), female BMI (n = 4302), female smoking (n = 4290), parity (n = 4365), infertility diagnosis (n = 4765), type of treatment (n = 4842) and center (n = 4842); some analyses additionally included gestational age (n = 4368) and sex of the child (n = 4833). MAIN RESULTS AND THE ROLE OF CHANCE: No statistically significant associations between blastocyst assessment scores (transfer day, developmental stage, TE, ICM) and preterm birth (8.3%) or birthweight (mean 3461.7 g) were found. The adjusted association between blastocysts with a TE score of C and a TE score of A and length at birth (mean 51.6 cm) were statistically significant (adjusted mean difference 0.4 cm (95% CI: 0.02; 0.77)). Blastocysts transferred with developmental stage score 5 compared to blastocysts transferred with score 3 had a 34% increased probability of being a boy (odds ratio (OR) 1.34 (95% CI: 1.09; 1.64). Further, TE score B blastocysts compared to TE score A blastocysts had a 31% reduced probability of being a boy (OR 0.69 (95% CI: 0.60; 0.80)). LIMITATIONS, REASONS FOR CAUTION: It is possible that some residual confounding remains. WIDER IMPLICATIONS OF THE FINDINGS: Blastocyst selection during ART does not appear to introduce any negative effects on obstetric outcome. Therefore, clinicians and patients can be reassured that the assessment scores of the selected blastocyst will not in themselves pose a risk of preterm birth or affect birthweight and the length at birth. STUDY FUNDING/COMPETING INTEREST(S): Unrestricted grant from Gedeon Richter Nordics AB, Sweden. None of the authors have any competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Rapid flocculation and settling of positively buoyant microplastic and fine-grained sediment in natural seawater.

Interactions between microplastic (MP) and fine-grained suspended sediment in natural waters are important for the environmental fate of plastic particles. Estuaries are transitional areas between freshwater and open marine systems and are recognized as important accumulation zones for MPs. However, there is a knowledge gap on the processes driving the sedimentation of MPs in estuaries, especially with regard to positively buoyant MPs. Here we show from settling tube experiments that positively buoyant and non-spherical MP HDPE particles in different size-fractions (63-500 µm) and concentrations (1 and 5 mg l-1) rapidly flocculate and settle with natural fine-grained sediment in natural seawater. Our results demonstrate that flocculation is a key process for the vertical transport of MP in estuaries. The implication is that land-based sources of positively buoyant HDPE MP transported by rivers will likely settle and accumulate in estuarine environments and thereby increase the concentration of MP in the benthic zone.

Colonic Health in Hospitalized Horses Treated with Non-Steroidal Anti-Inflammatory Drugs - A Preliminary Study.

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause right dorsal colitis, but longitudinal clinical studies are lacking. This study investigates whether NSAID treated horses develop right dorsal colonic pathology in a clinical setting. Non-gastrointestinal hospitalized horses treated with NSAIDs >4 days, and untreated hospital-owned teaching horses and non-gastrointestinal client-owned hospitalized horses were included. All horses were monitored over time with clinical examinations (focusing on presence of colic, depression, reduced appetite, unstructured feces), ultrasonographic intestinal wall measurements, fecal occult blood tests (semi-quantitative results), and blood analysis (total protein and albumin concentrations, white blood cell and neutrophil counts). Outcomes were recorded as "ultrasonographically thickened right dorsal colon (RDC) walls", "colitis" and "right dorsal colitis". Findings over time were compared to baseline values and to control horses. Seventeen NSAID treated horses and 5 controls were included. NSAID treated horses developed thickened RDC walls (4/9), and subclinical and mild colitis (9/11) and right dorsal colitis (4/10), whereas all control horses remained healthy. The first changes were identified on treatment day 2. RDC walls of treated horses were significantly thicker compared to their own baseline values and compared to control horses. In conclusion, presumptive colon pathology was identified with a high incidence, starting early in the course of treatment, but with low severity. Appropriate monitoring should be advised throughout NSAID treatment. Additional research for noninvasive diagnostic tests for colon pathology is required.

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

BACKGROUND: Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. AIM: To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. METHODS: A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. RESULTS: A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. CONCLUSIONS: According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding.

The incidence of congenital malformations and variations in Göttingen minipigs.

Knowledge of the incidence of spontaneous congenital abnormalities is critical for the accurate interpretation of findings in teratogenicity studies in any species. In this paper, results of the examination of 1739 neonatal Göttingen Minipigs are presented. Over the 2-year period under consideration, the incidence of external and visceral malformations was less than 0.2 and 0.1%, respectively. The most common external malformations were syndactyly, limb hyperflexion, domed head and scoliosis. The most common internal malformations were undescended testes, ventricular septal defect, diaphragmatic hernia and atrial septal defects. Pentadactyly and variation in the aortic arch's bifurcation (absent truncus bicaroticus) were the most common variations. These data will help support the use of the Göttingen Minipig as a non-rodent species in embryofetal development studies where concerns persist about the availability of background data.

Hexokinase redistribution in vivo.

Heterogenous stock mice in addition to mice selectively bred to maximally differ in their severity of alcohol withdrawal seizures (withdrawal seizure-resistant (WSR) and withdrawal seizure-prone (WSP] were used to provide evidence in favor of the importance of the rapidly changing distribution of brain hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) (HK). An ischemic response at 15, 30, 60 and 120 s after killing showed a decreasing cerebellar cytosolic HK concentration of 31%, 15%, 14% and 10% while the cerebral concentrations were 23%, 13%, 13% and 14%, respectively. WSR and WSP mice given an acute i.p. dose of 4 g/kg of alcohol showed opposite HK responses. Cytosolic HK in WSR mice decreased 18.5%, while WSP mice showed an increase of 20.3% over paired saline-injected controls. When ischemia was allowed to proceed in WSP mice following an in vivo alcohol treatment, cytosolic HK decreased in parallel to mice not given alcohol. These data suggest that alcohol can cause an HK redistribution in vivo which could play a role in the differing sensitivities of WSR and WSP mice to alcohol related seizures.

Complement activation upon binding of mannan-binding protein to HIV envelope glycoproteins.

OBJECTIVE: Retroviruses can activate the complement system in the absence of antibodies, and the purpose of this study was to examine whether the serum collection, mannan-binding protein (MBP), could mediate such complement activation. DESIGN: Virus envelope proteins gp120 and gp110 from HIV-1 and HIV-2 were incubated in microtitre wells coated with anti-gp120 or anti-gp110 antibodies. After further incubation with serum, complement activation was measured as deposition of complement factor C4 and C3 onto the wells. Deposited C4 and C3 were detected with enzyme-labelled antibodies. Normal human serum depleted of endogenous lectins by affinity chromatography was used as the complement source. Serum from C1q-deficient patients was used in some experiments. Complement activation was then assessed with and without prior addition of MBP to the wells. Complement activation was also correlated with the quantity of endogenous MBP in a number of normal sera. RESULTS: Complement activation by HIV envelope glycoproteins was found to be mediated by the binding of MBP to carbohydrates on natural envelope protein produced in virus-infected cells, as well as on glycosylated recombinant envelope proteins produced in insect cells. Non-glycosylated recombinant envelope proteins produced in Escherichia coli did not induce this type of complement activation. CONCLUSIONS: Activation of the classical complement pathway by retrovirus envelope proteins can be initiated by the binding of MBP to carbohydrate side chains of envelope glycoproteins.

Mannan-binding lectin (MBL) in chickens: molecular and functional aspects.

Mannan-binding lectin (MBL) is a serum collectin (i.e. mosaic protein with collagenous and lectin domains) involved in the innate immune defence against various microbes. In vitro studies indicate that MBL exerts its function by binding to the microbial surface through its carbohydrate recognition domains followed by direct opsonization or complement activation via the MBL associated serine proteases MASP-1 and MASP-2. In Aves (i.e. chickens), as in man, only one MBL form has been found, while traditional laboratory animals (i.e. mouse and rat) have two MBL forms in serum. MBL has been extensively studied in mammals but recently also in Aves. This review summarizes the present knowledge of MBL in chickens and compares it to the situation in mammals.

No evidence for decreasing semen quality in four birth cohorts of 1,055 Danish men born between 1950 and 1970.

OBJECTIVE: To compare the quality of semen in 1,055 Danish men born between 1950 and 1970 who are assumed to represent a random sample of the Danish male population of fertile age. DESIGN: Retrospective review of data on semen quality at the time of the female partner's first IVF treatment. SETTING: The Fertility Clinic, Odense University Hospital, Odense, Denmark. PATIENT(S): One thousand fifty-five male partners of women with tubal infertility who were referred for IVF treatment consecutively during the period 1990-1996. INTERVENTION(S): Analysis of the semen samples delivered and used in connection with the couples' first IVF treatment. MAIN OUTCOME MEASURE(S): Year of birth, age at time of sample collection, sperm concentration, and semen volume. RESULT(S): The mean sperm concentration (+/- SD) was 183.7 x 10(6) mL and the mean semen volume (+/- SD) was 3.9 mL. A considerable variation in both parameters was found from year to year, but no significant change occurred in either parameter throughout the entire period. When four birth cohorts were compared, a later year of birth was not associated with any change in sperm concentration or semen volume. CONCLUSION(S): Sperm concentration and semen volume were not related to year of birth, indicating that sperm quality has not changed in the Danish male population during the last 20-30 years.

Human menopausal gonadotropin versus recombinant follicle-stimulating hormone in normogonadotropic women down-regulated with a gonadotropin-releasing hormone agonist who were undergoing in vitro fertilization and intracytoplasmic sperm injection: a prospective randomized study.

OBJECTIVE: To evaluate clinical and endocrinological effects of intranasal (IN) vs. subcutaneous (SC) GnRH-a for pituitary down-regulation combined with hMG vs. rFSH. DESIGN: Prospective, randomized study. SETTING: University hospital, IVF unit. PATIENT(S): Three hundred seventy-nine normogonadotropic women eligible for IVF or ICSI. INTERVENTION(S): Randomization to intranasal (IN) or SC GnRH-a and to hMG or rFSH. MAIN OUTCOME MEASURE(S): Oocytes retrieved, embryos developed, clinical pregnancy, and delivery rates. Serum hormone concentrations on stimulation days 1 (S1) and 8 (S8), and oocyte pick-up (OPU) day. RESULT(S): After randomization, four groups were formed: IN/hMG (n = 100), IN/FSH (n = 98), SC/hMG (n = 89), and SC/FSH (n = 92). Mean number of oocytes retrieved and of transferable and transferred embryos were similar in the four groups. Clinical pregnancy rate per started cycle was significantly higher in the IN/HMG group than in the SC/FSH group (P<.05) and was intermediate in the two remaining groups. Se-LH on S8 in the two SC groups was significantly lower than in the two IN groups. Se-E2 on S8 in the SC/FSH group was significantly lower than in the other three groups. CONCLUSION(S): The clinical and endocrinological outcome in IVF and ICSI-treated normogonadotropic women is significantly influenced by mode of down-regulation as well as gonadotropin formulation.

Acrokeratosis paraneoplastica (Bazex' syndrome).

A 63-year-old man had acrokeratosis paraneoplastica (Bazex' syndrome) characterized by violaceous erythema and scaling of the fingers, toes, nose, and aural helices. Severe nail dystrophy was present. Extensive examination of the patient for malignant neoplasms a few months after the initial appearance of the skin changes disclosed no abnormalities, but one year after onset, an epidermoid carcinoma of the lung was found.

DSLET (D-ser2-leu5-enkephalin-Thr6) produces analgesia on the hot plate by mechanisms largely different from DAGO and morphine-like opioids.

Fifteen generations of selective breeding were used to produce lines (strains) of mice which differ markedly from one another in levorphanol-induced antinociception on the hot plate assay. These are the high antinociceptive response (HAR) and low antinociceptive response (LAR) selection lines, which now differ by over 5-fold in the i.p. dose of levorphanol doubling control (no drug or saline) latency scores. We sought to determine if these large genetically-mediated differences in antinociceptive sensitivity bred into these selection lines with i.p. levorphanol would generalize equally to a series of enkephalin analogues known to differ in their selectivity for mu and delta opioid receptors. DAGO (D-ala2, MePhe4, Gly-ol5 enkephalin), a highly mu selective agent, produced a 67-fold difference between HAR and LAR mice in the slopes of the dose-response curves on the hot plate assay, while DSLET (D-ser2, leu enkephalin Thr6), a delta selective agent, only produced a 5.4-fold difference via the i.c.v. route. DADLE (D-ala, D-ser enkephalin) a slightly delta preferring ligand, was found to be intermediate (17.4-fold difference). These findings demonstrate that selective breeding has been quite successful in altering those genes which control analgesia due to mu selective agents, while relatively little change has occurred in those genes which control analgesia due to delta agonists. Thus, analgesia mediated by the former has been genetically dissociated from analgesia mediated by the latter, implying that DAGO has mechanisms of action largely dependent of DSLET on the hot plate assay. These findings are consistent with the contention that the mu receptor mediates analgesia produced by DAGO, while a different receptor (presumably delta) mediates much of the analgesic effects of DSLET.

Ethanol and nitrous oxide produce withdrawal-induced convulsions by similar mechanisms in mice.

Twenty generations of selective breeding were used to produce lines (strains) of mice which differ markedly from one another in ethanol physical dependence development as indexed by handling-induced convulsions (HIC) induced by withdrawal from ethanol. These withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) selection lines now differ by over 10-fold in HIC scores after equivalent exposure to intoxicating levels of ethanol via inhalation. Since handling-induced convulsions can be readily elicited following withdrawal from nitrous oxide, we sought to determine if the very large differences in ethanol withdrawal-induced HIC bred into these selection lines would generalize to nitrous oxide. Following a 60 min exposure to 75% nitrous oxide (in O2), a greater than 10-fold difference in HIC scores, and a 2-fold difference in tremor incidence was seen upon withdrawal in WSP vs. WSR mice. These findings closely parallel those seen with ethanol, and demonstrate that a large degree of commonality exists in the genes and the mechanisms determining these withdrawal signs. HIC elicited by nitrous oxide withdrawal were readily suppressed by ethanol, and HIC elicited by ethanol withdrawal were promptly suppressed by 75% nitrous oxide in WSP mice. Nitrous oxide also suppressed HIC and tremor associated with nitrous oxide withdrawal.

Ethanol and diazepam withdrawal convulsions are extensively codetermined in WSP and WSR mice.

Selective breeding was used to produce lines of mice which differ markedly in their genetically-mediated vulnerability to handling-induced convulsions (HIC) associated with the ethanol withdrawal syndrome. These are known as the ethanol withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) selection lines. As a result of 5 generations of selective breeding with ethanol, a 3.4-fold difference between WSP and WSR mice was seen in HIC associated with ethanol withdrawal. When diazepam was used as the dependence-producing drug, a 2.4-fold difference emerged. After 6 more generations of selective breeding with ethanol, an approximate 10-fold difference was seen with ethanol, while with diazepam, this difference in HIC scores was also about 10-fold. This close parallel between ethanol and diazepam indicates that physical dependence on both drugs, as indexed by handling-induced convulsions, is extensively codetermined by the same genes, and thus by the same mechanisms, in these selectively-bred mice.

Serum levels of chicken mannan-binding lectin (MBL) during virus infections; indication that chicken MBL is an acute phase reactant.

Mannan-binding lectin (MBL) is a serum collectin which is believed to be an opsonin of the innate immune defence against various microorganisms. MBL is a minor acute phase reactant in man. We investigated the concentration of serum MBL in chickens infected with infectious bronchitis virus (IBV) and infectious laryngotracheitis virus (ILTV). The concentration of serum MBL increased about twofold (from approximately 6 to 12 microg/ml) due to these viral infections. The concentration peaked 3-7 days after infection with IBV, and 3-5 days after ILTV infection, depending on the ILTV strain used. The increased levels returned to normal values 6-10 days after infection. The results indicated that MBL is a minor acute phase reactant in chickens.

Where are the mu receptors that mediate opioid analgesia? An autoradiographic study in the HAR and LAR selection lines.

One line (strain) of mouse has been selectively bred in our laboratory for 15 generations to exhibit a very high sensitivity to levorphanol-induced analgesia on the hot plate assay (HAR or high antinociceptive response line). Concurrently, a second line (LAR or low antinociceptive response line) has been bred in the opposite direction, i.e., to exhibit a very low sensitivity under the same conditions. This has resulted in a 7-fold difference in sensitivity between HAR and LAR mice as a result of changes in gene frequency. Receptor autoradiographic studies with 3H-DAGO were carried out in the central gray to find receptor populations differing greatly in density between HAR and LAR mice to parallel their in vivo sensitivity differences: such receptors would then be implicated in mediating in vivo analgesia. The caudal portions of the dorsal raphe nucleus (DRN) showed 1.5- to 2-fold differences in density of mu sites, while the periaqueductal gray (PAG) showed relatively small differences. These results strongly suggest that mu receptors in a portion of the DRN are involved in mediating analgesia due to systemically administered opioids in this population of mice.

[Group B streptococcal infection in adults]. / Gruppe B-streptokokinfektioner hos voksne.

Three cases of infection with Streptococcus agalactiae, or Lancefield group B beta-haemolytic streptococcus (GBS), in adults are described and the literature is reviewed. During a period of 14 years the incidence of GBS-disease in adults aged above 15 years has increased in Denmark. The most common clinical presentations of GBS-disease in adults are puerpural fever, bacteraemia without evident focus, skin or soft-tissue infection, pneumonia, urosepsis and meningitis, preceded by a few days of influenza-like symptoms. The features of this fulminant disease include rapid development of multiple organ dysfunction syndrome (MODS) with renal impairment, adult respiratory distress syndrome (ARDS) and, in many patients, also cardiovascular instability. The therapy includes parenteral antibiotics, usually with high doses of benzylpenicillin, and symptomatic treatment. GBS-disease in both infants and adults may be prevented by the development of effective GBS-vaccines.

[Awareness anesthesia--an anesthesiologic dilemma]. / Huskeanaestesi--et anaestesiologisk dilemma.

Awareness is a traumatic unintentional event during general anaesthesia. Awareness during anaesthesia is a condition which ranges from a state of alertness to deep anaesthesia with partly preserved senses. Awareness can be divided into four groups, depending on the state of alertness and accessibility of the memories after anaesthesia. Diagnostics and follow-up is complicated when awareness with an impaired recall occurs. We conclude that the incidence of awareness has decreased during the last three decades from approximately 1.5% to 0.2% during general surgery. In clinical practice there is no method for the detection of depth of anaesthesia and no anaesthetic technique that prevents awareness during anaesthesia. Guidelines to further reduce the incidence are suggested. Instant treatment of the condition may relieve the acute trauma and reduce the sequelae. We suggest a postoperative visit to ensure quality development for recording and treatment of awareness during anaesthesia.

[An ambulatory service staffed with military physicians in a rural district. Experiences from a period of 6 years]. / En militaer laegeassisteret udrykningsordning i et landdistrikt. Erfaringer over en seksårsperiode.

A local rendez-vous arrangement is described retrospectively in which the medical officer on duty at the infirmary, Oksbøl military camp participated in the ambulance service and the prehospital treatment of acutely ill patients. The military ambulance supports the civilian ambulance service in the municipality of Blåvandshuk, Western Jutland. This arrangement was carried out in 430 cases and 399 patients were brought to hospital. More than 14% of the services did not result in transportation. Forty-seven percent of the services were due to accidents and 30% to illness. In 16% of all cases the response-time was less than five minutes. All the patients were classified according to the Oksbøl-score. Injuries were diagnosed in 48% and cardiovascular disease in 19%. Sixty-seven percent were treated immediately by the military ambulance. This arrangement has improved the prehospital treatment of acutely ill patients by using pre-existing resources from a military camp. We propose further cooperation between civilian health authorities and the Danish Armed Forces' Health Services when planning the prehospital services.

[Air travel and deep venous thrombosis]. / Flyrejse og dyb venøs trombose.

A case of deep venous thrombosis (DVT) in a woman with polio sequelae is reported. The patient presented with classical sign of DVT, probably caused by air travel. Guidelines for air travellers in order to prevent the economy class syndrome are presented.