No association of spastic paraparesis genes in PSEN1 Alzheimer's disease with spastic paraparesis

Familial Alzheimer's disease due to presenilin 1 (PSEN1) mutations shows considerable phenotypic variability with differences in neuropathology and neurological symptoms. Spastic paraparesis is a common neurological phenotype associated with Alzheimer's disease arising from PSEN1 mutations. To investigate whether known genes that cause spastic paraparesis could act as Alzheimer's disease-modifier genes, we sequenced nine spastic paraparesis genes in three Alzheimer's disease families with PSEN1 exon 9 deletions. We did not observe any correlation of polymorphisms or mutations in the nine spastic paraparesis genes with the variable phenotype seen in families with Alzheimer's disease and spastic paraparesis. These results suggest a need for a continuing search for genes that cause the phenotypic variation in Alzheimer's disease and spastic paraparesis.     

Prognostic factors for the success rate of embryo freezing

To find some prognostic factors for the outcome of frozen-thawed cycles, we have retrospectively analysed all frozen pre-embryos that were thawed during 1993 and 1994 at two in-vitro fertilization (IVF) units in Sweden. Supernumerary pre-embryos were frozen from 551 oocyte retrievals and these resulted in 660 frozen-thawed cycles which lead to 623 thawed embryo transfers. The outcome of these transfers was 137 clinical pregnancies with a pregnancy rate of 22% per frozen-thawed embryo transfers. Women <40 years of age had a higher birth rate than those > or =40 years, 19 and 5% respectively (P < 0.01). Transfers with two and three pre-embryos resulted in pregnancy rates of 23 and 27%, respectively, compared with 14% for transfer of one embryo. A pregnancy resulting from the initial embryo transfers had a predictive value for results of the subsequent frozen-thawed cycle. Embryo grade and cleavage stage at the time of freezing was important for the survival of the frozen-thawed pre-embryos. The pregnancy rate was not influenced by the cleavage stage, but a tendency toward a lower pregnancy rate was seen for the embryos with lower grading. To conclude, cryopreservation seems to be beneficial in women <40 years of age, who have supernumerary pre-embryos of good quality for freezing and of which at least two can be transferred.      

Usability and acceptability of an automated respiratory rate counter to assess children for symptoms of pneumonia: A cross-sectional study in Ethiopia

Aim

Manually counting respiratory rate (RR) is commonly practiced by community health workers to detect fast breathing, an important sign of childhood pneumonia. Correctly counting and classifying breaths manually is challenging, often leading to inappropriate treatment. This study aimed to determine the usability of a new automated RR counter (ChARM) by health extension workers (HEWs), and its acceptability to HEWs, first-level health facility workers (FLHFWs) and caregivers in Ethiopia.

Methods

A cross-sectional study was conducted in one region of Ethiopia between May and August 2018. A total of 131 HEWs were directly observed conducting 262 sick child consultations after training and 337 after 2 months. Usability was measured as adherence to the WHO requirements to assess fast breathing and device manufacturer instructions for use (IFU). Acceptability was measured through semi-structured interviews.

Results

After 2 months, HEWs were shown to adhere to the requirements in 74.6% consultations; an increase of 18.6% after training (P < .001). ChARM is acceptable to users and caregivers, with HEWs suggesting that ChARM increased client flow and stating a willingness to use ChARM in future.

Conclusion

Further research on the performance, cost-effectiveness and implementation of this device is warranted to inform policy decisions in countries with a high childhood pneumonia burden.

     

Absorption and motility of the bypassed human ileum

The authors assessed absorption and motility of the human ileum after a prolonged period of disuse. In eight patients with ulcerative colitis, a manometric-catheter assembly was placed via the ileostomy into the unused portion of distal ileum two months after ileal pouch-anal anastomosis and temporary diverting loop ileostomy. The distal ileum was perfused at 5 ml/min with an isosmotic solution of either sodium chloride or ileal chyme diluted with sodium chloride for three hours before and three hours after a meal on two consecutive days. Absorption was measured, single and clustered pressure waves were identified and quantitated with the aid of a computer program, and a motility index was calculated. Mean absorption ± S.E.M. of both perfusates was poor on day 1 (–10±2 ml/25 cm × 30 min), and the meal induced no ileal motor response. By day 2, however, absorption of both perfusates was much improved (–1±2 ml/25 cm × 30 min; P<0.05), and the number of discrete clustered contractions and the motility index now clearly increased after the meal (2.6±0.6 vs. 7.2±1.0 clustered waves/hr; 7.5±0.5 vs. 9.7±0.2 motility units/30 min;P<0.05).The conclusion was that absorption and motility of the human ileum were impaired after two months of disuse, but that ileal absorption and motility improved one day after the introduction of isosmotic ileal perfusates.Supported in part by USPHS NIH Grants DK34988, DK18278 and DK07198, and the Mayo Foundation.     

Ectopic jejunal pacemakers and enterogastric reflux after Roux gastrectomy: effect of intestinal pacing

The aims of this study were to determine whether ectopic pacemakers are present in the Roux limb of dogs after vagotomy and Roux gastrectomy, whether these pacemakers lead to enterogastric reflux, and whether abolishing the pacemakers with electric pacing might correct such reflex, were it to occur. In five dogs that had undergone gastric vagotomy and Roux gastrectomy and five dogs that had undergone gastric vagotomy and Billroth I gastrectomy (controls), myoelectric activity of the Roux limb or duodenum was recorded during saline infusion (154 mmol/L NaCl) or nutrient (Meritene) infusion into the limb or the duodenum. Reflux of infusate into the stomach was determined via a gastric cannula. Tests in Roux dogs were done with and without limb pacing. Roux dogs showed ectopic pacemakers in the Roux limb that drove the pacesetter potentials of the limb in a reverse, or orad, direction during 76% of the recordings; Billroth dogs rarely had such pacemakers (p less than 0.001). Enterogastric reflux occurred in both groups of dogs but was greater during phase III of the interdigestive migrating myoelectric complex in Roux dogs (12% +/- 6%) than in Billroth dogs (3% +/- 1%; p less than 0.05). Pacing abolished the ectopic pacemakers in the Roux dogs and reduced enterogastric reflux from 12% +/- 6% to 3% +/- 2% when phase III was present (p less than 0.05). In conclusion, the Roux limb was driven by ectopic pacemakers that contributed to, but were not solely responsible for, jejunogastric reflux. Pacing abolished the ectopic pacemakers and decreased reflux when phase III was present in the limb.     

Ectopic jejunal pacemakers and gastric emptying after Roux gastrectomy: effect of intestinal pacing

The aims of this study were to determine whether ectopic pacemakers are present after meals in the Roux limbs of dogs after vagotomy and Roux gastrectomy, whether these pacemakers slow gastric emptying of liquids or solids, and whether abolishing the pacemakers with electric pacing might speed any slow emptying that occurs. In six dogs that underwent vagotomy and Roux gastrectomy and in four dogs that underwent vagotomy and Billroth gastrectomy (controls), myoelectric activity of the Roux limb or duodenum was measured during gastric emptying of a 500 kcal mixed meal of 99mTc-labeled cooked egg and 111In-labeled milk. Roux dogs were tested with and without pacing of the Roux limb. Roux dogs showed ectopic pacemaker in the Roux limb that drove the pacesetter potentials of the limb in a reverse, or orad, direction during 57% of the postprandial recordings. Billroth dogs had no ectopic pacemakers (p less than 0.05). Liquids emptied more slowly in Roux dogs (half-life (t1/2) = 121 +/- 15 minutes) than in Billroth dogs (t1/2 = 43 +/- 9 minutes; p less than 0.05), but solids emptied similarly in both groups of dogs (t1/2 approximately 8 hours). Pacing the Roux limb abolished the ectopic pacemakers, restored the slow emptying of liquids to the more rapid rate found in the Billroth dogs (t1/2: paced Roux, 72 +/- 15 minutes; Billroth, 43 +/- 9 minutes; p greater than 0.05) and did not change emptying of solids. The conclusion was that ectopic pacemakers present in the Roux limb after vagotomy and Roux gastrectomy drove the limb in a reverse direction and slowed emptying of liquids after the operation. The defect was corrected by pacing the Roux limb in a forward direction.     

Heat‐shock–mediated conditional regulation of hedgehog/gli signaling in zebrafish

Background: Hedgehog (Hh) signaling is required for embryogenesis and continues to play key roles postembryonically in many tissues, influencing growth, stem cell proliferation, and tumorigenesis. Systems for conditional regulation of Hh signaling facilitate the study of these postembryonic Hh functions. Results: We used the hsp70l promoter to generated three heat‐shock–inducible transgenic lines that activate Hh signaling and one line that represses Hh signaling. Heat‐shock activation of these transgenes appropriately recapitulates early embryonic loss or gain of Hh function phenotypes. Hh signaling remains activated 24 hr after heat shock in the Tg(hsp70l:shha‐EGFP) and Tg(hsp70l:dnPKA‐BGFP) lines, while a single heat shock of the Tg(hsp70l:gli1‐EGFP) or Tg(hsp70l:gli2aDR‐EGFP) lines results in a 6‐ to 12‐hr pulse of Hh signal activation or inactivation, respectively. Using both in situ hybridization and quantitative polymerase chain reaction, we show that these lines can be used to manipulate Hh signaling through larval and juvenile stages. A ptch2 promoter element was used to generate new reporter lines that allow clear visualization of Hh responding cells throughout the life cycle, including graded Hh responses in the embryonic central nervous system. Conclusions: These zebrafish transgenic lines provide important new experimental tools to study the embryonic and postembryonic roles of Hh signaling. Developmental Dynamics 242:529–539, 2013. © 2013 Wiley Periodicals, Inc.