Effects of the muscarinic agonist pilocarpine on vigilance states and locomotor activity in ring doves

Cholinergic systems play a significant role in regulating a variety of behavioral functions in mammals and birds. The aim of this work is to study the effects of the muscarinic agonist pilocarpine on behavioral states by visual inspection and electroencephalographic recording; also, locomotor activity was continuously recorded by infrared interruption system in ring doves. The current results in birds demonstrated that the muscarinic agonist pilocarpine (1 and 3 mg/kg, i.p.) primarily induced theta activity in addition to promote passive waking, while diminished active waking, the EEG slow wave rhythm and REM sleep in ring doves. The locomotor activity recorded continuously in ring doves diminished after pilocarpine treatment, which was in good agreement with the observed reduction of active waking derived of the EEG study. Altogether, the current results are similar to the effects of pilocarpine previously reported in mammals. In conclusion, hippocampal theta rhythm in birds suggests that this rhythm is an ancestral property of hippocampal function and similar cholinergic mechanisms regulate vigilance states and theta generation in mammals and birds.     

Cavitary pneumonia in an AIDS patient caused by an unusual Bordetella bronchiseptica variant producing reduced amounts of pertactin and other major antigens

Although Bordetella bronchiseptica can infect and colonize immunocompromised humans, its role as a primary pathogen in pneumonia and other respiratory processes affecting those patients remains controversial. A case of cavitary pneumonia caused by B. bronchiseptica in an AIDS patient is presented, and the basis of the seemingly enhanced pathogenic potential of this isolate (designated 814) is investigated. B. bronchiseptica was the only microorganism recovered from sputum, bronchoalveolar lavage fluid, and samples taken through the protected brush catheter. Unlike previous work reporting the involvement of B. bronchiseptica in cases of pneumonia, antibiotic treatment selected on the basis of in vitro antibacterial activity resulted in clearance of the infection and resolution of the pulmonary infiltrate. Although isolate 814 produced reduced amounts of several major antigens including at least one Bvg-activated factor (pertactin), the molecular basis of this deficiency was found to be BvgAS independent since the defect persisted after the bvgAS locus of isolate 814 was replaced with a wild-type bvgAS allele. Despite its prominent phenotype, isolate 814 displayed only a modest yet a significant deficiency in its ability to colonize the respiratory tracts of immunocompetent rats at an early time point. Interestingly, the antibody response elicited by isolate 814 in these animals was almost undetectable. We propose that isolate 814 may be more virulent in immunocompromised patients due, at least in part, to its innate ability to produce low amounts of immunogenic factors which may be required at only normal levels for the interaction of this pathogen with its immunocompetent natural hosts.     

Electroencephalogram functional connectivity between rat hippocampus and cortex after pilocarpine treatment

The muscarinic agonist pilocarpine has been shown to increase the duration and total number of episodes presenting theta rhythm—simultaneously in hippocampus and cortex—in rats during the waking states. Theta waves are suggested to be involved in the flow of information between hippocampus and cortex during memory processes. This work investigates this functional interdependence using the spectral and phase synchronization analysis of the electroencephalogram (EEG) theta band recorded in these brain structures of rats after pilocarpine treatment. Pilocarpine was used at doses devoid of epilepticus-like seizures effects in conscious freely moving rats. The results showed that pilocarpine administration significantly increased the relative theta power during the waking states in the cortex, but not in the hippocampus of rats. Additionally, the EEG coherence between the hippocampal EEG theta band and that arising at the frontal cortex increased after pilocarpine treatment but only during the waking states. This result reveals an increase of the linear correlation between the theta waves of these two brain structures after pilocarpine treatment during the waking states. Moreover, phase synchronization results showed an effective phase locking with non-zero phase difference between hippocampus and frontal cortex theta waves that remained after pilocarpine treatment. Therefore, pilocarpine seems to reinforce the neural transmission waves from the hippocampus toward the cortex during waking. In conclusion, the present EEG study could suggest an effect of the muscarinic cholinergic agonist pilocarpine on the hippocampal-cortical functional connectivity.     

Maternal heart rate changes during labour

Objectives

Labour and delivery represent a considerable effort for pregnant women. Lack of aerobic fitness may limit pushing efforts during childbirth and represents increased cardiovascular strain and risk. Increasing prevalence of sedentary behaviour and lack of aerobic fitness may reduce heart rate reserve during labour.

Study design

We quantified maternal heart rate reserve (maximum heart rate minus resting heart rate) of 30 healthy pregnant women during labour and delivery and related it to habitual daily physical activity levels quantified during the third pregnancy trimester by the Pregnancy Physical Activity Questionnaire.

Results

Heart rates during labour reached values similar to those observed during moderate to heavy physical exercise. During active pushing one out of five women reached heart rates more than 90% of their heart rate reserve (188 ± 7 beats per min). Half of the women reached more than 70% of heart rate reserve (172 ± 14 beats per min). Physically inactive women used more of their heart rate reserve as physically more active women (87 ± 20% vs. 65 ± 12%, upper and lower tertile respectively, p < 0.05).

Conclusions

Use of heart rate reserve for the effort of labour is increased in physically inactive women and may potentially limit the intensity and duration of pushing efforts. Such higher cardiovascular strain in physically less active women may represent increased cardiovascular risk during labour.     

The human ovarian teratocarcinoma cell line PA-1 demonstrates a single translocation: analysis with fluorescence in situ hybridization, spectral karyotyping, and bacterial artificial chromosome microarray

Cell lines derived from tumors contain numerous chromosomal aberrations and are the focus of study in tumor evolution. The ovarian teratocarcinoma cell line PA-1 demonstrates a single chromosomal aberration: a reciprocal t(15;20)(p11.2;q11.2). A complete molecular genetic analysis was undertaken to characterize this cell line. The PA-1 cell line was studied with fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), bacterial artificial chromosome (BAC) microarray, and Western blotting. Amplification of 20q is frequently implicated in both breast and ovarian cancer; this region contains a number of oncogenes including MDM2, ZNF217, and the ovarian tumor marker WFDC2 (alias HE4). FISH revealed gene amplification of AIB1 (now known as NCOA3) but not STK15 (now known as AURKA). Immunoblot analysis demonstrated 3.6-fold overexpression of the AIB1 protein product, but no elevation of the STK15. BAC cancer gene microarray analysis showed gene amplification of > or =1.20 for five oncogenes. The presence of a consistent single change in PA-1, the t(15;20)(p11.2;q11.2), suggests that the aberration is significant with respect to the transformation status of the cell line. This translocation appears to cause overexpression of AIB1 (and perhaps other proteins), which may provide an immortalizing effect on this cell line.     

Targeted BRCA1/2 population screening among Ashkenazi Jewish individuals using a web-enabled medical model: An observational cohort study

PurposeThis study aimed to evaluate uptake and follow-up using internet-assisted population genetic testing (GT) for BRCA1/2 Ashkenazi Jewish founder pathogenic variants (AJPVs).MethodsAcross 4 cities in the United States, from December 2017 to March 2020, individuals aged ≥25 years with ≥1 Ashkenazi Jewish grandparent were offered enrollment. Participants consented and enrolled online with chatbot and video education, underwent BRCA1/2 AJPV GT, and chose to receive results from their primary care provider (PCP) or study staff. Surveys were conducted at baseline, at 12 weeks, and annually for 5 years.ResultsA total of 5193 participants enrolled and 4109 (79.1%) were tested (median age = 54, female = 77.1%). Upon enrollment, 35.1% of participants selected a PCP to disclose results, and 40.5% of PCPs agreed. Of those tested, 138 (3.4%) were AJPV heterozygotes of whom 21 (15.2%) had no significant family history of cancer, whereas 86 (62.3%) had a known familial pathogenic variant. At 12 weeks, 85.5% of participants with AJPVs planned increased cancer screening; only 3.7% with negative results and a significant family history reported further testing.ConclusionAlthough continued follow-up is needed, internet-enabled outreach can expand access to targeted GT using a medical model. Observed challenges for population genetic screening efforts include recruitment barriers, improving PCP engagement, and increasing uptake of additional testing when indicated.     

Two unusual manifestations of aortic aneurysms

Pain and pulsation are common presenting features of aortic aneurysms. Massive hematemasis and ureteral obstruction represent rare clinical presentations. This report describes a patient with massive hematemesis in whom a thoracic aneurysm ruptured into the esophagus, and a second patient in whom a large abdominal aortic aneurysm caused bilateral ureteral obstruction.     

Shielding islets with human amniotic epithelial cells enhances islet engraftment and revascularization in a murine diabetes model

Hypoxia is a major cause of considerable islet loss during the early posttransplant period. Here, we investigate whether shielding islets with human amniotic epithelial cells (hAECs), which possess anti‐inflammatory and regenerative properties, improves islet engraftment and survival. Shielded islets were generated on agarose microwells by mixing rat islets (RIs) or human islets (HI) and hAECs (100 hAECs/IEQ). Islet secretory function and viability were assessed after culture in hypoxia (1% O₂) or normoxia (21% O₂) in vitro. In vivo function was evaluated after transplant under the kidney capsule of diabetic immunodeficient mice. Graft morphology and vascularization were evaluated by immunohistochemistry. Both shielded RIs and HIs show higher viability and increased glucose‐stimulated insulin secretion after exposure to hypoxia in vitro compared with control islets. Transplant of shielded islets results in considerably earlier normoglycemia and vascularization, an enhanced glucose tolerance, and a higher β cell mass. Our results show that hAECs have a clear cytoprotective effect against hypoxic damages in vitro. This strategy improves β cell mass engraftment and islet revascularization, leading to an improved capacity of islets to reverse hyperglycemia, and could be rapidly applicable in the clinical situation seeing that the modification to HIs are minor.     

Conjunctivitis with Regional Lymphadenopathy in a Trainee Microbiologist

We report a case of conjunctival tuberculosis in a trainee microbiologist caused by direct inoculation. The resident strain was analyzed by DNA fingerprinting, and an identical pattern was found in an isolate from sputum handled by the resident. After 6 months of treatment, the patient was cured.