Development of properly-polarized trophoblast stem cell-derived organoids to model early human pregnancy.

The development of human trophoblast stem cells (hTSC) and stem cell-derived trophoblast organoids has enabled investigation of placental physiology and disease and early maternal-fetal interactions during a stage of human pregnancy that previously had been severely restricted. A key shortcoming in existing trophoblast organoid methodologies is the non-physiologic position of the syncytiotrophoblast (STB) within the inner portion of the organoid, which neither recapitulates placental villous morphology in vivo nor allows for facile modeling of STB exposure to the endometrium or the contents of the intervillous space. Here we have successfully established properly-polarized human trophoblast stem cell (hTSC)-sourced organoids with STB forming on the surface of the organoid. These organoids can also be induced to give rise to the extravillous trophoblast (EVT) lineage with HLA-G + migratory cells that invade into an extracellular matrix-based hydrogel. Compared to previous hTSC organoid methods, organoids created by this method more closely mimic the architecture of the developing human placenta and provide a novel platform to study normal and abnormal human placental development and to model exposures to pharmaceuticals, pathogens and environmental insults. Motivation: Human placental organoids have been generated to mimic physiological cell-cell interactions. However, those published models derived from human trophoblast stem cells (hTSCs) or placental villi display a non-physiologic "inside-out" morphology. In vivo , the placental villi have an outer layer of syncytialized cells that are in direct contact with maternal blood, acting as a conduit for gas and nutrient exchange, and an inner layer of progenitor, single cytotrophoblast cells that fuse to create the syncytiotrophoblast layer. Existing "inside-out" models put the cytotrophoblast cells in contact with culture media and substrate, making physiologic interactions between syncytiotrophoblast and other cells/tissues and normal and pathogenic exposures coming from maternal blood difficult to model. The goal of this study was to develop an hTSC-derived 3-D human trophoblast organoid model that positions the syncytiotrophoblast layer on the outside of the multicellular organoid.

The use of a Swedish telephone medical advice service by the elderly - a population-based study.

OBJECTIVE: The present study aimed to describe contact made by the elderly to Sweden's nationwide medical helpline, Healthcare Guide 1177 by Phone (HGP). Other objectives were to study potential gender differences and the association between different HGP referral levels and acute visits to hospital-based emergency departments and acute visits to primary care centres. DESIGN: De-identified data from recorded calls to HGP was extracted for analysis (n = 7477 for the oldest age group). Information about acute visits to emergency departments and to primary care reception was extracted from the patient administration system. SETTING: Västerbotten County, Sweden. SUBJECTS: Patients over 80 years. MAIN OUTCOME MEASURES: Calling and visiting frequencies for different age groups as well as reasons for contact and individual recommendations. RESULTS: The utilisation rate of the telephone advice service for the oldest age group was high, with an incidence rate of 533 per 1000 person-years. Women had a 1.17 times higher incidence rate compared with men. The most common reason for contact was drug-related questions (17% of all contacts). Calls that were recommended to care by a medical specialist correlated with total emergency department visits (r = 0.30, p < 0.05) and calls that were given advice correlated with acute primary healthcare visits (r = 0.38, p = 0.005). CONCLUSION: The high utilisation of the telephone advice service by the elderly gives the telephone advice service a unique ability to function as a gatekeeper to further healthcare. Our data suggest that with the telephone advice service's present guidelines, a significant proportion of all calls are being directed to further medical help. The high frequency of drug-related questions raises concerns about the elderly's medication regimens. Key points Patients over 80 years of age had a high utilisation of the telephone medical advice service compared with other age groups. Drug-related questions were the most common reason for contact. A significant proportion of all calls made resulted in further heatlhcare contacts.

Accidental farm injuries in children.

Eighty-seven children with 88 farm injuries presented to our emergency room in Rochester, Minn, from November 1974 to July 1985. Seventy-four accidents (84.1%) occurred in boys, and 14 (15.9%) in girls. Ages ranged from 1 to 16 years. Farm machines involved included corn augers in 37 accidents (42.0%); tractors, 22 (25.0%); power takeoffs, ten (11.4%); conveyor belts, five (5.7%); and miscellaneous, 14 (15.9%). Fractures and lacerations were the most common injuries, occurring in 55 (62.5%) and 30 (34.1%), respectively. Significant long-term disability occurred in 36 (40.9%). Eleven children required multiple reconstructive surgical procedures; two died. Preventive measures that can be employed by physicians, family members, educators, and legislators are discussed.

Primary hyperparathyroidism in Northern Sweden.

Three hundred and eleven patients with presumed hyperparathyroidism were operated upon between the years 1961 and 1983 at the two surgical clinics in Northern Sweden equipped with pathologic facilities. Eighty per cent were women. All of the patients were hypercalcemic. Parathyroid hormone (PTH) levels were elevated in 66 per cent of the patients. The correlation between serum calcium and PTH levels was only 0.38. Serum creatinine levels were normal in 92 per cent of the patients while renal concentrating ability was depressed in 79 per cent. The main patient symptoms were fatigue, mental disturbances and renal stones. Eighteen per cent were asymptomatic at the time of the operation. Most patients were diagnosed during in-hospital investigations. Many were also found to be hypercalcemic at regular outpatient controls. At operation, adenomas were found in 80 per cent, different kinds of hyperplasia in 15 per cent, normal histologic finding in 4 per cent, while cancer was found in less than 1 per cent of the patients. At follow-up study, 79 per cent were normocalcemic while 3 per cent were hypocalcemic and 11 per cent were still hypercalcemic--7.5 per cent were lost to follow-up study. Nine patients had a permanent paralysis of the recurrent laryngeal nerve.

Dietary and species influence on potential of plasma to stimulate differentiation and lipid accumulation in cultured adipocyte precursors.

Sera and plasma from different species and from rats of various dietary statuses were compared with regard to effects on proliferation, glycerophosphate dehydrogenase (GPDH) activity, and lipid-filing of rat adipocyte precursors converting to adipocytes in primary cell culture. All of the tested sera and plasma samples were comparably supportive of cell multiplication, but their effects on elevation of GPDH activity (a key event in adipocyte differentiation) and lipid-filling varied greatly. Plasma supported a much greater increase in GPDH activity than serum, while serum from cats supported a much lower increase than serum from humans, calves, goats, or rats. Dietary status of rats did not affect the potential of plasma to support GPDH activity, but did affect plasma support of lipid-filing. A higher than normal degree of lipid-filling was promoted by plasma from rats fed a high-fat, high-sugar diet, while a lower than normal degree was promoted by plasma from fasted rats. Lipid-filling was also found to vary in response to changes in content of very low density lipoprotein (VLDL) in human plasma. This suggests that the influence of diet on the potential of plasma to promote adipocyte lipid-filling may be mediated by the effect of diet on plasma VLDL. The absence of a diet-dependent effect of plasma either on multiplication of adipocyte precursors or on degree of elevation of GPDH activity leaves unresolved the mechanism by which diet affects adipocyte production in animals.

Temporal patterns in psychophysiological activation in rotating shift workers--A follow-up field study one year after an increase in nighttime work.

The study concerned the long-term effects of a weekly rotating day-night shift schedule on circadian functions. It was performed 1 h after the introduction of an increase in nighttime work and was a follow-up of a study performed one month after the change of workhours. Fourteen male typesetters were observed in connection with the first, fourth and seventh nightshifts of the "night week" and the two dayshifts of the "day week." Measurements were taken of body temperature and self-rated activation during awake periods, of adrenaline excretion during work and sleep, and of choice-reaction time during work. The results showed that a different pattern of variation in circadian functions was present 1 h after the increase in nighttime work when compared to the pattern one month after the increase. The change in pattern consisted mainly of a general flattening of the curves during both day and night work, although some changes from the beginning to the end of the nightshift week could still be noticed.

Long-term adjustment of circadian rhythms to a rotating shiftwork schedule.

This investigation is a further study of the long-term effects of a weekly rotating day-night shift schedule on circadian rhythms. It was performed 3 a after the introduction of an increase in nighttime work. Six male typesetters were observed in connection with the beginning and end of the nightshift week and in connection with their free days in the "day week." Measurements were taken of body temperature during both the awake and sleep periods and of self-rated activation. For the same subjects a comparison was also made of variations in awake temperatures and self-related activation after one month, one year and three years on the new shift schedule. Results showed that after 3 a of experience the awake temperature curves had a flattened shape in connection with both the beginning and end of the nightshift week and also during the free days. During sleep there was however a short-term adjustment of the temperature curves within the nightshift week. Comparisons over years revealed significant changes in the course of variation in body temperature during both night and day work, while no significant changes were found for self-related activation. The possibility that experience has a differential influence upon the phase adjustment of temperature maxima compared to minima was discussed.

Attempted suicides-35 years afterward.

Most follow-up studies of suicides are made after a relatively short period of time. The present study involved 229 attempted suicides (93 men and 136 women) hospitalized during the years 1933-1942. It was possible to trace 96.8% of the men and 95.6% of the women. An earlier investigation 0 to 12 years after hospitalization showed that in the first 4 years 9 men (9.7%) and 5 women (3.7%) had committed suicide. The observation time for the present study ranges from 21 to 42 years, with a mode of 35 years. It was found that an additional 4 men and 7 women had committed suicide in the interim-in the cases of 2 men and 6 women, 15 years or more after the initial attempt. This incidence of suicide so long after the original attempt, at least in the case of the women, statistically exceeds the expected incidence. In the time now elapsed, 10.9% of the study sample (14% of the men and 8.8% of the women) have taken their own lives.