Ethical issues related to brain organoid research.

This review provides a snapshot of the current ethical issues related to research with human brain organoids. The issues fall into the following main themes: research oversight; human biomaterials procurement and donor consent; translational delivery; animal research; and organoid consciousness and moral status. Each of these areas poses challenges for researchers, bioethicists, regulators, research institutions, and tissue banks. However, progress can be made if these parties build on past experiences with stem cell research, ethics, and policy, but adapted accordingly to new aspects of brain organoid research.

Electrophoretic deposition of polymethylmethacrylate and composites for biomedical applications.

For the first time, an electrophoretic deposition (EPD) method has been developed for the deposition of polymethylmethacrylate (PMMA) and PMMA-alumina films for biomedical implant applications. The proposed biomimetic approach was based on the use of a bile salt, sodium cholate (NaCh), which served as a multifunctional solubilizing, charging, dispersing and film-forming agent. Investigations revealed PMMA-Ch- and PMMA-alumina interactions, which facilitated the deposition of PMMA and PMMA-alumina films. This approach allows for the use of a non-toxic water-ethanol solvent for PMMA. The proposed deposition strategy can also be used for co-deposition of PMMA with other functional materials. The PMMA and composite films were tested for biomedical implant applications. The PMMA-alumina films showed statistically improved metabolic results compared to both the bare stainless steel substrate and pure PMMA films. Alkaline phosphatase (ALP) activity affirmed the bioactivity and osteoconductive potential of PMMA and composite films. PMMA-alumina films showed greater ALP activity than both the PMMA-coated and uncoated stainless steel.

Right atrial stretch induces renal nerve inhibition and c-fos expression in parvocellular neurones of the paraventricular nucleus in rats.

The paraventricular nucleus of the hypothalamus plays a pivotal role in the regulation of plasma volume. Part of the response to an increase in volume load is an inhibition of renal sympathetic nerve activity. The present experiments were designed to determine which subnuclei of the paraventricular nucleus are involved in this sympatho-inhibitory response. Experiments were performed on anaesthetised rats. Activated neurones were recognised by the expression of the early gene c-fos, identified by immunohistochemical labelling of its protein product Fos. Plasma volume loading with 4 % Ficoll 70, using an infusion-withdrawal procedure (2 ml over 1 min) repeated 15 times over 1 h revealed a total of 775 +/- 101 (n = 6) Fos-positive neurones scattered throughout both the magnocellular and parvocellular subnuclei. In comparison, sustained hypertension resulted in 452 +/- 56 (n = 3) Fos-positive neurones similarly distributed, whereas a normotensive control group (n = 3) displayed 115 +/- 18 Fos-positive neurones. Because of this lack of a specific effect we used a more selective stimulation of right atrial receptors via a balloon placed at the junction of the superior vena cava and the right atrium so it did not impede venous return. Inflation of the balloon inhibited renal sympathetic nerve activity (36 +/- 5 %, n = 7) and repetitive inflation over 1 h resulted in c-fos activation of a small number of neurones (54 +/- 14) located only in the parvocellular subnuclei. Whether these are inhibitory interneurones acting within the paraventricular nucleus, or spinally projecting neurones which inhibit or excite renal sympathetic activity by an action in the spinal cord remains to be determined.

Does intraoperative hetastarch administration increase blood loss and transfusion requirements after cardiac surgery?

UNLABELLED: Hetastarch is used for intravascular volume expansion in cardiac surgery. Studies show conflicting effects of intraoperative hetastarch administration on postoperative bleeding. Hetastarch was routinely used for volume expansion during cardiovascular surgeries at our institution until its use was discontinued intraoperatively. We performed a retrospective chart review on patients undergoing primary coronary artery bypass grafting, valve repair or replacement requiring cardiopulmonary bypass (n = 444), 234 of which received intraoperative hetastarch and 210 did not. There was no difference in demographics, cardiac surgery, or cardiopulmonary bypass duration between the two groups. Blood loss for 0-4 h postoperatively was 377 +/- 244 mL in the group not receiving hetastarch compared with 515 +/- 336 mL in the group that received hetastarch (P < 0.001). For 0-24 h postoperatively, blood loss was 923 +/- 473 mL versus 1,283 +/- 686 mL in the absence and presence of hetastarch, respectively (P < 0.001). Allogeneic transfusion requirements (cryoprecipitate, fresh frozen plasma, and platelets) were larger in the hetastarch group (all P < 0.001). Nearly all (99%) patients in the hetastarch group received less than the manufacturer's recommended dose (20 mL/kg) of hetastarch. IMPLICATIONS: Our large retrospective study suggests that intraoperative use of hetastarch in primary cardiac surgery with cardiopulmonary bypass may increase bleeding and transfusion requirements. A large prospective study is needed to determine if intraoperative administration of hetastarch should be avoided during cardiovascular surgery.

Paraventricular neurones elicit a volume expansion-like change of activity in sympathetic nerves to the heart and kidney in the rabbit.

The role of the paraventricular nucleus (PVN) of the hypothalamus in the cardiovascular response induced by blood volume expansion was examined in anaesthetised rabbits, in which simultaneous recordings were made from a renal sympathetic nerve and one of other sympathetic nerves, the inferior cardiac nerve, a splanchnic nerve and an adrenal nerve. Activation of PVN neurones, by discrete injections (25-100 nl) of d,l-homocysteic acid (DLH, 0.2 M) produced one main pattern of sympathetic nerve activity accompanying a pressor response (57-86 % of PVN sites). This was a decrease in renal sympathetic activity (27 +/- 12 %) and an increase in splanchnic (60 +/- 12 %), adrenal (31 +/- 9 %) and cardiac (42 +/- 8 %) sympathetic activity. Sites in the PVN from which these combinations of nerve activity were obtained were not confined to a specific subnucleus. An increase in renal sympathetic activity which was reversed to a decrease by reducing the volume of DLH injected was obtained at 10 sites in the PVN. These sites were mainly located in the dorsal parvocellular subnucleus. Varying combinations of sympathetic activation were obtained at a minority of sites. It is concluded that the PVN can evoke a differential pattern of sympathetic discharge which may be functionally significant in the control of blood volume regulation, as it mimics that seen on acute volume expansion.

Control of sympathetic outflows by the hypothalamic paraventricular nucleus.

1. The functional role of the paraventricular nucleus (PVN) has been examined by studying its connections with cardiovascular neurons in the medulla and spinal cord and its influence on activity in several sympathetic nerves. 2. Chemical stimulation of neurons within the PVN can elicit pressor responses and can excite reticulo-spinal vasomotor neurons in the rostral ventrolateral medulla (RVLM). 3. The PVN-RVLM excitation is blocked by kynurenic acid applied iontophoretically in the vicinity of RVLM-spinal neurons, suggesting this is a glutamate-dependent pathway. 4. Electrical stimulation of PVN neurons evoked action potentials in RVLM neurons after 27 ms with a small variability. 5. Anterograde and retrograde labelling of PVN and RVLM neurons revealed PVN terminals closely associated with RVLM-spinal neurons and showed that the PVN is connected to the spinal cord via three pathways. 6. Chemical activation of PVN neurons can produce a pattern of activation of cardiovascular neurons similar to that occurring in defence against plasma volume expansion. 7. It is concluded that the PVN connections with the RVLM and spinal cord are important to a role in defending against life-threatening disturbances.

Job satisfaction of nursing assistants in long-term care.

A study of job satisfaction of nursing assistants (NAs) was conducted in two nursing homes (one in a relatively poor urban neighborhood, the other in an affluent suburban neighborhood). When it comes to job content, NAs were more satisfied than dissatisfied. However, they are less satisfied with working conditions. The NAs of the suburban facility were less satisfied than those of the urban facility. Managers need to focus more on the work environment than on job content to develop a more satisfied work force.

Complications of warfarin therapy monitored by the International Normalized Ratio versus the prothrombin time ratio.

The objective of our study was to determine the rates of bleeding complications and thromboembolic events in patients receiving oral anticoagulant therapy monitored with the prothrombin time (PT) ratio versus therapy monitored with the International Normalized Ratio (INR) using a retrospective time-series study design. Over 650 patients enrolled in a large anticoagulation clinic were studied during two time periods corresponding to the use of the PT ratio versus the INR to guide anticoagulant therapy, with over 400 patient-years of follow-up for each time period. The rate of bleeding complications using the PT ratio to guide therapy was 6.7% (1.2% major, 5.5% minor) per patient-year, compared with 2.9% (0% major, 2.9% minor) using the INR (p = 0.02). The rate of thromboembolic complications was 1.0% using the PT ratio, compared with 0.2% using the INR (p = NS). Therapy monitored with the INR required 19.8 visits per year, compared with 20.7 visits per year using the PT ratio. We conclude that the INR should be used to monitor oral anticoagulant therapy in an effort to reduce bleeding complications while maintaining an acceptable rate of thromboembolic events.

Pacemaker lead fracture associated with weightlifting: a report of two cases.

Two cases of pacemaker lead fracture associated with weight-lifting are presented. This is a rare association which has only recently been described in the literature. In both cases, the pacemaker lead was fractured between the clavicle and the first rib, suggesting crush injury. The chest X-ray, pacemaker telemetry with measurement of lead impedance, and pacemaker reprogramming were all helpful in management.

Repression, derepression and activation of nitrogenase in Azotobacter vinelandii.

Ammonium ion repressed nitrogenase in cells fixing N2 gas. Immunological tests and electrophoresis in various gels show that components I (Fe-Mo-S protein) was completely repressed by ammonium, whereas component II (Fe-S protein) apoprotein was not markedly affected. Component II from ammonium-grown cells, however, was inactive since it did not cross react with component I to reduce C2H2 to C2H4. The inactive component II apoprotein is immunologically identical to its active counterpart from cells fixing N2. Identical protein patterns were also observed in various gel-electrophoresis systems. Oxygen-inactivated component II may be reactivated with FeSo4. This salt is preferable to ferrous ammonium sulphate which inactivated component I. Immunodiffusion under aerobic conditions shows that purified component I is composed of aggregated and non-aggregated forms which are antigenically distinct. The aggregate was dissociated by treatment with sodium dodecyl sulphate (SDS) into a single antigenic species which was further resolved into two subunits on SDS disc polyacrylamide gel electrophoresis.