Perinatal and infant outcome of fetuses with prenatally diagnosed hyperechogenic kidneys.

OBJECTIVE: Hyperechogenic kidneys are a relatively rare antenatal finding, which can generate significant parental anxiety due to uncertain prognosis. We report on the perinatal and infant outcomes of a large cohort of fetuses with antenatally diagnosed hyperechogenic kidneys. METHODS: This was a retrospective analysis of all cases diagnosed prenatally with hyperechogenic kidneys between 2002 and 2017 in a large tertiary fetal medicine unit. Hyperechogenicity was defined as kidney parenchyma with greater echogenicity than that of the liver. Pregnancy, pathological and postnatal outcomes were collected from hospital and general practitioner records up to 1 year of age. Abnormal renal outcome was defined as elevated creatinine beyond 6 months of age, hypertension requiring medication or major kidney surgery, such as nephrectomy. Severe abnormal renal outcome was defined as the need for dialysis or kidney transplant at any stage. RESULTS: Three-hundred and sixteen fetuses with hyperechogenic kidneys were identified at a mean gestational age of 21 (range, 13-37) weeks. The majority of cases (97%) had bilateral hyperechogenic kidneys. In the 265 cases with available follow-up data, other associated renal tract abnormalities were identified prenatally in 36%, concomitant extrarenal structural abnormalities in 39% and abnormal karyotype in 15% of cases. Of the 316 included cases, 139 did not survive, including 105 terminations of pregnancy, five intrauterine deaths and 29 early neonatal deaths. Only 4.3% (6/139) of these fetuses had isolated hyperechogenic kidneys while 28.1% (39/139) had associated multiple renal tract abnormalities alongside hyperechogenic kidneys and over two-thirds (67.6%; 94/139) had concomitant extrarenal abnormalities. Of the 177 cases that survived beyond 1 month of age, outcome data were available in 126. Of these, based on the antenatal findings, 60 (47.6%) cases had isolated hyperechogenic kidneys, 56 (44.4%) had associated renal structural abnormalities and 10 (7.9%) had additional extrarenal abnormalities. Considering renal outcome alone, kidney function was abnormal in 13 (21.7%), 10 (17.9%) and 0 (0%) infants in these three groups, respectively, although concurrent pathology clearly affected global outcome in the more complex cases. Neonatal mortality of 1.6% was observed in the isolated renal hyperechogenicity group. The presence of oligohydramnios or abnormal renal volume was not associated significantly with abnormal renal function (odds ratio (OR), 2.32 (99% CI, 0.54-10.02) and OR, 0.74 (99% CI, 0.21-2.59), respectively) in this group. CONCLUSIONS: Hyperechogenic kidneys are often complicated by associated renal tract and extrarenal abnormalities, aberrant karyotype and genetic disease, and these factors have a greater effect on overall outcome than does kidney echogenicity. The renal outcome of fetuses with isolated hyperechogenic kidneys is good generally, with over 70% of cases having normal renal function postpartum. Importantly, for prognostic counseling, all of the fetuses in this non-selected series with isolated hyperechogenic kidneys and normal amniotic fluid levels had normal renal outcome in infancy. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Medical care of adults with Down Syndrome a clinical guideline

Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients. To develop an evidence-based clinical practice guideline for adults with Down syndrome. The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Library, and the TRIP Database, searched from January 1, 2000, to February 26, 2018, with an updated search through August 6, 2020. Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework, in January 2019, the 13-member Workgroup and 16 additional clinical and scientific experts, nurses, patient representatives, and a methodologist developed clinical recommendations. A statement of good practice was made when there was a high level of certainty that the recommendation would do more good than harm, but there was little direct evidence. From 11 295 literature citations associated with 10 PICO questions, 20 relevant studies were identified. An updated search identified 2 additional studies, for a total of 22 included studies (3 systematic reviews, 19 primary studies), which were reviewed and synthesized. Based on this analysis, 14 recommendations and 4 statements of good practice were developed. Overall, the evidence base was limited. Only 1 strong recommendation was formulated: screening for Alzheimer-type dementia starting at age 40 years. Four recommendations (managing risk factors for cardiovascular disease and stroke prevention, screening for obesity, and evaluation for secondary causes of osteoporosis) agreed with existing guidance for individuals without Down syndrome. Two recommendations for diabetes screening recommend earlier initiation of screening and at shorter intervals given the high prevalence and earlier onset in adults with Down syndrome. These evidence-based clinical guidelines provide recommendations to support primary care of adults with Down syndrome. The lack of high-quality evidence limits the strength of the recommendations and highlights the need for additional research.

Contributions of cellular and humoral immunity of Galleria mellonella larvae in defence against oral infection by Bacillus thuringiensis.

In this study the cellular and humoral immune reactions of the Greater wax moth Galleria mellonella have been investigated during bacterial infection caused by oral administration of Bacillus thuringiensis. Two different dose strengths were investigated to assess the contribution of immune parameters to induced Bt resistance. Low-dose (sublethal LC15) infection resulted in significantly elevated haemolymph phenoloxidase and lysozyme-like activity, enhanced phagocytic activity of haemocytes, and increased encapsulation responses in infected larvae at 48 and 72 h post infection. Higher doses of Bt (half-lethal LC50) also triggered significantly elevated haemolymph phenoloxidase and lysozyme-like activity, but decreased the coagulation index and activity of phenoloxidase in haemocytes of infected larvae. In both types of infection, the pool of circulating haemocytes became depleted. The importance of cellular and humoral immune reactions in induced insect resistance to intestinal bacterial infection Bt is herein discussed.

Bacterial septicaemia in prerecruit edible crabs, Cancer pagurus L.

Juvenile edible crabs, Cancer pagurus L., were surveyed from Mumbles Head and Oxwich Bay in South Wales, UK, and the number of heterotrophic bacteria and vibrios in the hemolymph was determined. The percentage of crabs with hemolymph containing bacteria was variable over the survey with higher numbers of animals affected in summer than in winter. Post-moult crabs contained significantly higher numbers of heterotrophic bacteria in the hemolymph than pre- and intermoult animals. Crabs with cuticular damage to the gills also had significantly higher numbers of bacteria in the hemolymph. Crabs were found to have a high prevalence of infection by the dinoflagellate, Hematodinium. Such animals had significantly fewer bacteria in the blood in comparison with Hematodinium-free animals. Of the 463 crabs surveyed, only 3 individuals had hemolymph containing 2000 + CFU mL(-1). Based on 16S rRNA gene sequences, two of these crabs contained a Vibrio pectenicida-like isolate, while the other had a mixed assemblage of vibrios. Although 59% of the crabs surveyed had culturable bacteria in the hemolymph, the majority only had small numbers (<2000 CFU mL(-1) ), suggesting that such infections may be of limited importance to the sustainability of the crab fishery in this region.

Thoroughbred racehorse mitochondrial DNA demonstrates closer than expected links between maternal genetic history and pedigree records.

The potential future earnings and therefore value of Thoroughbred foals untested in the racing arena are calculated based on the performance of their forebears. Thus, lineage is of key importance. However, previous research indicates that maternally inherited mitochondrial DNA (mtDNA) does not correspond to maternal lineage according to recorded pedigree, casting doubt on the voracity of historic pedigrees. We analysed mtDNA of 296 Thoroughbred horses from 33 maternal lineages and identified an interesting trend. Subsequent to the founding of the Thoroughbred breed in the 16th century, well-populated maternal lineages were divided into sub-lineages. Only six in 10 of the Thoroughbreds sampled shared mitochondrial haplotype with other members of their maternal lineage, despite having a common maternal ancestor according to pedigree records. However, nine in 10 Thoroughbreds from the 103 sub-lineages sampled shared mtDNA with horses of their maternal pedigree sub-lineage. Thus, Thoroughbred maternal sub-lineage pedigree represents a more accurate breeding record than previously thought. Errors in pedigrees must have occurred largely, though, not exclusively, at sub-lineage foundation events, probably due to incomplete understanding of modes of inheritance in the past, where maternal sub-lineages were founded from individuals, related, but not by female descent.

More than a colour change: insect melanism, disease resistance and fecundity.

A 'dark morph' melanic strain of the greater wax moth, Galleria mellonella, was studied for its atypical, heightened resistance to infection with the entomopathogenic fungus, Beauveria bassiana. We show that these insects exhibit multiple intraspecific immunity and physiological traits that distinguish them from a non-melanic, fungus-susceptible morph. The melanic and non-melanic morphs were geographical variants that had evolved different, independent defence strategies. Melanic morphs exhibit a thickened cuticle, higher basal expression of immunity- and stress-management-related genes, higher numbers of circulating haemocytes, upregulated cuticle phenoloxidase (PO) activity concomitant with conidial invasion, and an enhanced capacity to encapsulate fungal particles. These insects prioritize specific augmentations to those frontline defences that are most likely to encounter invading pathogens or to sustain damage. Other immune responses that target late-stage infection, such as haemolymph lysozyme and PO activities, do not contribute to fungal tolerance. The net effect is increased larval survival times, retarded cuticular fungal penetration and a lower propensity to develop haemolymph infections when challenged naturally (topically) and by injection. In the absence of fungal infection, however, the heavy defence investments made by melanic insects result in a lower biomass, decreased longevity and lower fecundity in comparison with their non-melanic counterparts. Although melanism is clearly correlated with increased fungal resistance, the costly mechanisms enabling this protective trait constitute more than just a colour change.

The cosmopolitan maternal heritage of the Thoroughbred racehorse breed shows a significant contribution from British and Irish native mares.

The paternal origins of Thoroughbred racehorses trace back to a handful of Middle Eastern stallions, imported to the British Isles during the seventeenth century. Yet, few details of the foundation mares were recorded, in many cases not even their names (several different maternal lineages trace back to 'A Royal Mare'). This has fuelled intense speculation over their origins. We examined mitochondrial DNA from 1929 horses to determine the origin of Thoroughbred foundation mares. There is no evidence to support exclusive Arab maternal origins as some historical records have suggested, or a significant importation of Oriental mares (the term used in historic records to refer to Middle East and western Asian breeds including Arab, Akhal-Teke, Barb and Caspian). Instead, we show that Thoroughbred foundation mares had a cosmopolitan European heritage with a far greater contribution from British and Irish Native mares than previously recognized.

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct.

The development of clinically beneficial myocardial gene therapy has been slowed by reliance on the use of viral carriers and non-physiologic, constitutive gene expression. To specifically address these issues, we have developed a non-viral gene carrier, water-soluble lipopolymer (WSLP), and an ischemia-inducible plasmid construct expressing vascular endothelial growth factor (VEGF), pRTP801-VEGF, to treat myocardial ischemia and infarction. Rabbits underwent ligation of the circumflex artery followed by injection of (a) an ischemia-inducible VEGF gene construct in a WSLP carrier; (b) a constitutively expressed, or unregulated, SV-VEGF gene construct in a WSLP carrier; (c) WSLP carrier alone; or (d) no injection therapy. Following 4 weeks treatment, ligation alone resulted in infarction of 48+/-7% of the left ventricle. With injection of WSLP carrier alone, 49+/-6% of the left ventricle was infarcted (P=NS). The constitutively expressed gene construct, SV-VEGF, reduced the infarct size to 32+/-7% of the left ventricle (P=0.007). The ischemia-inducible gene construct, RTP801-VEGF, further reduced the infarct size to 13+/-4% of the left ventricle (P<0.001). The use of a non-viral carrier to deliver an ischemia-inducible VEGF construct is effective in the treatment of acutely ischemic myocardium.

Mosquito midguts and malaria: cell biology, compartmentalization and immunology.

The malaria parasite Plasmodium has an absolute requirement for both a vertebrate and a mosquito host in order to complete its life cycle, and its interactions with the latter provide the focus for this review. The mosquito midgut represents one of the most challenging environments for the survival and development of Plasmodium, and is thus also one of the most attractive sites for novel targeted malaria control strategies. During their attempts to cross the midgut epithelium en route to the salivary glands, motile ookinetes are swiftly detected and labelled by mosquito recognition factors and targeted for destruction by a variety of immune responses that recruit killing factors both from the midgut and from other tissues in the surrounding body cavity. The exact interplay between these factors and the parasite is highly species- and strain-specific, as are the timing and the route of parasite invasion. These features are paramount to determining the success of the infection and the vector competence of the mosquito. Here we discuss recent advances in genomic analyses, coupled with detailed microscopical investigations, which are helping to unravel the identity and roles of the major players of these complex systems.

A novel approach to bilateral hand-assisted laparoscopic nephrectomy for autosomal dominant polycystic kidney disease.

PURPOSE: Laparoscopic nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) is technically challenging. We describe our technique and present our experience with a transperitoneal hand-assisted laparoscopic (HAL) technique using a standard vacuum curettage system to reduce the size of the kidneys thereby facilitating nephrectomy. MATERIALS AND METHODS: A retrospective review was completed of 10 consecutive patients undergoing bilateral HAL nephrectomy between March 2002 and October 2004 using the following technique. A hand port is positioned through a 6-7 cm periumbilical incision and port sites are placed at the midclavicular line (12 mm) and anterior axillary line (5 mm) on the side of the initial nephrectomy. After the renal vessels are divided and the kidney is completely mobilized a 12 mm curette is inserted through the medial port site. The Berkeley VC-10 Vacuum Curettage System (ACMI, Southborough, MA) is used to morcellate and aspirate the kidney providing a significant decrease in the overall size and allowing easy extraction through the midline incision. The procedure is repeated for the contralateral side. RESULTS: All 10 patients underwent successful bilateral HAL nephrectomy with a mean operative time of 194 minutes. The average length of stay was 4.7 days. Patients with renal allografts had stable function at the time of discharge. The average size of the kidneys removed was 717 g and average length was 19 cm. All patients did well postoperatively with complete resolution of their presenting symptoms. CONCLUSION: In patients with symptomatic ADPKD, bilateral HAL nephrectomy using the vacuum curettage system to minimize the size of the kidneys is fast, safe and effective.

Calreticulin enriched as an early-stage encapsulation protein in wax moth Galleria mellonella larvae.

To investigate the molecular mechanism of the early-stage encapsulation reaction in insects, we purified a 47kDa protein from injected beads into Galleria mellonella larvae. When a cDNA clone was isolated, the 47kDa protein showed high homology with Drosophila and human calreticulin. Western blotting analysis showed that the 47kDa protein was present in the hemocytes, but not in the plasma. When the early-stage encapsulated beads were coated with 47kDa protein antibody and reinjected into G. mellonella larvae, any further encapsulation reaction was inhibited. These results suggest that calreticulin is involved in non-self recognition in invertebrate cellular defense reactions.

Pathophysiology, diagnosis and management of prenatal upper tract dilatation.

Upper tract dilatation presenting as renal pelvis dilatation with or without ureteric dilatation is one of the more common abnormalities detected on prenatal ultrasound scanning. The majority of cases are due to pelvi-ureteric and vesico-ureteric junction anomalies, and vesico-ureteric reflux. Prenatal diagnosis with ultrasound may be aided by biochemical analysis of fetal blood and urine. The natural history of prenatally detected abnormalities remains under review. Precise diagnosis, and therefore prognosis, may not be made until after birth.

Role of superoxide and reactive nitrogen intermediates in Rhodnius prolixus (Reduviidae)/Trypanosoma rangeli interactions.

This study compares aspects of the superoxide, nitric oxide and prophenoloxidase pathways in Rhodnius prolixus hemolymph, measured in parallel, in response to Trypanosoma rangeli inoculation. Responses to two strains of T. rangeli, and two developmental forms, were studied, and the results obtained were correlated with the ability of the parasites to survive, multiply, and complete their life cycles in the hemolymph of the host. T. rangeli H14 strain parasites, which fail to complete their life cycle in Rhodnius by invading the salivary glands, stimulated high levels of superoxide and prophenoloxidase activity, which peaked 24 h after inoculation. Simultaneously, the concentration of hemolymph nitrites and nitrates increased, indicative of nitric oxide activity, but parasite numbers remained low. T. rangeli Choachi strain parasite inoculation also stimulated superoxide and prophenoloxidase activity, which, though significantly lower than the equivalent responses to the H14 strain, also peaked at 24 h. However, nitrate and nitrite levels in Choachi strain-inoculated hemolymph remained low, and this parasite strain multiplied rapidly, especially following peak superoxide activity, and eventually invaded the salivary glands for transmission to a vertebrate host. In both strains, short form epimastigotes stimulated greater superoxide and prophenoloxidase responses than long form epimastigotes. Injection of the NADPH oxidase inhibitor N-ethylmaleimide or the inducible nitric oxide synthase inhibitor S-methyl isothiourea sulfate caused significantly higher insect mortalities in groups of R. prolixus inoculated with either parasite strain compared with those of uninfected control insects. This indicates that both NADPH oxidase and nitric oxide synthase activity may be involved in the immune response of R. prolixus to infection by T. rangeli. Finally, Western blotting of R. prolixus hemocyte lysates revealed the presence of a protein immunologically related to the human NADPH oxidase complex, the initiator enzyme of the respiratory burst.

A novel form of rhodopsin kinase from chicken retina and pineal gland.

The G protein-coupled receptor kinases (GRKs) are important enzymes in the desensitization of activated G protein-coupled receptors (GPCR). Seven members of the GRK family have been identified to date. Among these enzymes, GRK1 is involved in phototransduction and is the most specialized kinase of the family. GRK1 phosphorylates photoactivated rhodopsin (Rho*), initiating steps in its deactivation. In this study, we found that chicken retina and pineal gland express a novel form of GRK that has sequence features characteristic of GRK1. However, unlike bovine GRK1 which is farnesylated, chicken GRK1 contains a consensus sequence for geranylgeranylation. Peptides corresponding to the C-terminal sequence of chicken GRK1 are geranylgeranylated by a cytosolic extract of chicken liver. Based on results of molecular cloning and immunolocalization, it appears that both rod and cone photoreceptors express this novel GRK1. These data indicate a larger sequence diversity of photoreceptor GRKs than anticipated previously.

In vitro superoxide activity in the haemolymph of the West Indian leaf cockroach, Blaberus discoidalis.

The respiratory burst is an NADPH oxidase-driven reduction of molecular oxygen to superoxide, which can occur in phagocytic cells as part of an antimicrobial defence, and is well documented among the vertebrates. This paper describes a process resembling the respiratory burst, which occurs in the haemolymph and haemocytes of the cockroach, Blaberus discoidalis. The in vitro reduction of nitroblue tetrazolium by superoxide to formazan was measured spectrophotometrically in B. discoidalis haemolymph in response to various immune elicitors. Nitroblue tetrazolium reduction was partly impeded in the presence of superoxide dismutase, a specific antioxidant which converts superoxide to hydrogen peroxide, as well as by chemicals known to inhibit the respiratory burst in vertebrates (trifluoperazine, diphenylene iodonium, and N-ethylmaleimide). This suggests the generation of superoxide anions by haemolymph as part of an immune response. Furthermore, formazan staining of elicitor-treated haemocytes was observed microscopically, with less intense staining in the presence of superoxide dismutase. Finally, respiratory burst inhibitors and superoxide dismutase enhanced the growth of E. coli incubated in whole haemolymph, implying a role for haemolymph-derived superoxide in antibacterial defence.

A randomized, prospective study comparing once-daily gentamicin versus thrice-daily gentamicin in the treatment of puerperal infection.

OBJECTIVE: The efficacy, safety, and antibiotic-related charges for once-daily gentamicin with twice-daily clindamycin were compared with those of thrice-daily dosing of these antibiotics. STUDY DESIGN: Patients with puerperal endometritis or with chorioamnionitis in labor assessed to be at risk for endometritis were randomized to receive gentamicin 4 mg/kg intravenously every 24 hours with clindamycin 1200 mg intravenously every 12 hours (experimental arm) or gentamicin 1.33 mg/kg intravenously and clindamycin 800 mg intravenously every 8 hours (conventional dosing interval arm). Primary outcomes included cure rates, mean length of treatment, antibiotic-related charges, and nephrotoxicity. Multiple logistic regression analysis was used to control for confounding variables. RESULTS: There were 135 and 137 patients randomized to the experimental and conventional interval arms, respectively. Cures were obtained in 94.1% and 87.6% of patients in the experimental and conventional arms, respectively (p = 0.06). The experimental arm had mean antibiotic charges of $250.79 versus $442.49 in the conventional arm (p < 0.0001). There was no permanent nephrotoxicity in either group. CONCLUSIONS: Once-daily gentamicin dosing with twice-daily clindamycin dosing is as efficacious and safe as the thrice-daily dosing of gentamicin and clindamycin for peripartum uterine infection. The experimental regimen results in substantial cost savings. The incidence of nephrotoxicity is low.