Kinetochore–microtubule interactions during cell division

Proper segregation of chromosomes during cell division is essential for the maintenance of genetic stability. During this process chromosomes must establish stable functional interactions with microtubules through the kinetochore, a specialized protein structure located on the surface of the centromeric heterochromatin. Stable attachment of kinetochores to a number of microtubules results in the formation of a kinetochore fibre that mediates chromosome movement. How the kinetochore fibre is formed and how chromosome motion is produced and regulated remain major questions in cell biology. Here we look at some of the history of research devoted to the study of kinetochore-microtubule interaction and attempt to identify significant advances in the knowledge of the basic processes. Ultrastructural work has provided substantial insights into the structure of the kinetochore and associated microtubules during different stages of mitosis. Also, recent in-vivo studies have probed deep into the dynamics of kinetochore-attached microtubules suggesting possible models for the way in which kinetochores harness the capacity of microtubules to do work and turn it into chromosome motion. Much of the research in recent years suggests that indeed multiple mechanisms are involved in both formation of the k-fibre and chromosome motion. Thus, rather than moving to a unified theory, it has become apparent that most cell types have the capacity to build the spindle using multiple and probably redundant mechanisms.     

Occurrence of disseminated intravascular coagulation in rat BNML leukaemia despite lack of leucocyte procoagulant activity.

Signs of disseminated intravascular clotting were observed during the development of BNML myelomonocytic leukaemia in rats, when the peripheral leucocyte count exceeded 20,000/microliters and more than 50% blasts were present in the circulation. BNML cells, harvested from blood and tested in appropriate systems, were found devoid of any procoagulant activity (PCA) even following prolonged in vitro incubation with endotoxin. Thus, it appears that these rat leukaemic cells share the same inability to express PCA which had been previously described in peripheral blood mononuclear cells from normal rats. Conceivably, in this rat model, leucocyte PCA does not represent a major trigger of intravascular coagulation and blood clotting is initiated by other, mainly plasmatic, pathways.     

A rapid immunoperoxidase assay for the detection of specific IgG antibodies to Chlamydia trachomatis

A technique, using indirect immunoperoxidase antibody (IPA), was developed for the detection of IgG antibody to Chlamydia trachomatis. The IPA technique employs glass slides with air-dried and acetone-fixed C trachomatis infected cells, which can be stored at -70 degrees C and used for several months. Antibody titres detected by IPA were comparable to those detected by the indirect fluorescent antibody technique.     

Aspirin and the prevention of experimental arterial thrombosis: difficulty in establishing unequivocal effectiveness

A trial of the efficacy of aspirin in the prevention of thrombotic occlusion of an "aortic loop" in rats was made simultaneously by two experimental surgeons. A relatively large dose of aspirin (80-100 mg/kg/day) was used, starting two days before operation. It appeared that aspirin was of limited benefit, reducing thrombotic occlusions by about 17% seven days after the insertion of the loop into the abdominal aorta. Although the average occlusion time was prolonged by about 17% in aspirin-treated animals, the separate trials gave no conclusive result. When the data from both operators were pooled, a statistically significant protection by aspirin was apparent (p = 0.02), by a two-tailed Student's t test. However, on using the powerful non-parametric randomization test, the occlusion times in control and aspirin-treated groups appeared not statistically different (p = 0.07). No significant difference was also found between control and treated groups when data were analyzed by X2 test. Independently of the statistical analysis, these data are quite similar to those obtained from aspirin trials in men surviving myocardial infarction. This finding points to the usefulness of the aorta loop as an animal model for arterial thrombosis.     

Surgeon experience contributes to improved outcomes in pancreatoduodenectomies at high risk for fistula development

BackgroundPancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood.MethodsThe fistula risk score was applied to identify high-risk patients (fistula risk score 7–10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003–2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models.ResultsEight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula rates decreased with escalating surgeon career pancreatoduodenectomy (–49.7%) and career length (–41.2%; both P < .001), as did transfusion and reoperation rates, postoperative morbidity index, and duration of stay. Great experience (≥400 pancreatoduodenectomies performed or ≥21-year-long career) was a significant predictor of clinically relevant pancreatic fistula prevention (odds ratio 0.52, 95% confidence interval 0.35–0.76) and was more often associated with pancreatojejunostomy reconstruction and prophylactic octreotide omission, which were both independently associated with clinically relevant pancreatic fistula reduction. A risk-adjusted performance analysis also correlated with experience. Moreover, minimizing blood loss (≤400 mL) significantly contributed to clinically relevant pancreatic fistula prevention (odds ratio 0.40, 95% confidence interval 0.22–0.74).ConclusionSurgeon experience is a key contributor to achieve better outcomes after high-risk pancreatoduodenectomy. Surgeons can improve their performance in these challenging situations by employing pancreatojejunostomy reconstruction, omitting prophylactic octreotide, and minimizing blood loss.     

Mental health services and the city: a neighbourhood-level epidemiological study

Journal of Public Health - Neighbourhood composition is considered a social determinant of mental health that can be addressed by policymakers to improve outcomes. Deprived neighbourhoods typically...     

Traumatic rupture of the thoracic aorta: Should one always operate immediately?

Although the traditional therapy for blunt traumatic rupture of the thoracic aorta (TRA) is immediate operative repair, there may be a selective role for delayed repair, particularly in patients with head trauma, respiratory failure, or cardiac dysfunction. The present study examines the hypothesis that TRA can be managed by selective delayed operative repair. Clinical data were collected from 59 consecutive patients with TRA at a regional trauma unit. All TRAs were at the aortic isthmus. Patients were retrospectively classified into three groups: group I (n=12) included patients who either arrived in extremis or rapidly became unstable during triage; group II (n=3) included patients who had no contraindications to early repair and underwent repair at the time of diagnosis; and group III (n=44) consisted of patients who because of concomitant injuries or sepsis required initial admission and management in the intensive care unit until their clinical status had improved sufficiently to allow for deliberate delayed operative repair of the TRA. The delay ranged from 1 day to 7 months. Eight patients have yet to undergo repair and remain well at follow-up from 1 to 4 years. Overall survival rates in groups I, II, and III were 17%, 100%, and 82%, respectively. The surgery-related mortality rate in group III was 10% (three patients). Only two (4.5%) patients in group III died as a result of a ruptured aorta within 72 hours of admission. In conclusion, contrary to surgical doctrine, TRA may not require immediate operative repair in all cases, but may instead be managed selectively depending on the patient's clinical status.     

The challenge for Cuba

The restrictions of a U.S. trade embargo and the collapse of the Soviet Union marked the beginning of a period of extreme economic hardship in Cuba. Economic adversity has had tremendous effects, both positive and negative, on all aspects of life on the Island, including environmental and public health.