Human pluripotent stem cell-derived cells endogenously expressing follicle-stimulating hormone receptors: modeling the function of an inactivating receptor mutation.

Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cyclic adenosine monophosphate (cAMP)-dependent signaling pathway and downstream mediators. To investigate protein-protein interaction partners of FSHR at resting state and upon FSH stimulation, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. Interestingly, while only WT FSHR interacted with FSH, insulin-like growth factor 1 receptor (IGF1R), for example, interacted with both WT and A189V FSHR upon FSH stimulation. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.

Training of medical staff positively influences postoperative pain management at home in children.

The aim of this study was to describe how parents manage their child's postoperative pain at home following day-case surgery. The incidence of pain, different analgesics used and problems related to administering medications were the main interests of the study. A postal questionnaire was sent to the parents of 275 children who were under 8 years of age and had undergone an ear, nose and throat (ENT) day-case operation. The questionnaire was sent to the parents a week after discharge from hospital. Altogether, the parents of 227 children answered the questionnaire (response rate 83%). The study was divided into two phases (preintervention and postintervention), and incorporated a training program for doctors and nurses between these two phases. The training program aimed to improve the treatment practices of postoperative pain in children. Seventy-eight per cent of the children in the preintervention study and 75% in the postintervention study experienced at least mild pain after discharge. The training program for doctors and nurses affected the home treatment practices of postoperative pain. The proportion of parents treating their children increased from 68% to 80% after the training program (p = 0.028). Many parents faced problems while treating their children; for example, 19% (n = 30) of the children refused to take their medicine, and suppositories were regarded to be an especially unpleasant dosage form. However, no serious adverse effects were reported. We conclude that due to the pain experienced at home by the great majority of children following day-case ENT operations, parents need information on how to manage their child's pain. A training program for doctors and nurses can improve the treatment of children's pain even at home. Since some children dislike suppositories, it would be worth considering the use of small tablets or mixtures instead.

The effects of a hospital staff training program on the treatment practices of postoperative pain in children under 8 years.

The widespread use of day case surgery for minor operations in children places increased emphasis on home care, parental responsibility and attention to suitable analgesia. This study evaluated a training program for doctors and nurses on postoperative analgesia in children by following up parental perceptions of pain relief after discharge. The main objective of our study was to determine the effects of a training program on treatment practices in the hospital and on the home care instructions provided. The study was carried out in two phases. A questionnaire was sent to parents of children aged under 8 years who had undergone a minor otorhinolaryngological operation (tonsillectomy, adenoidectomy, irrigation of maxillary sinus, insertion of grommets, or paracentesis) at the Day Case Unit in Kuopio University Hospital. The parents of 115 children returned the questionnaire in the preintervention study and those of 112 children in the postintervention study (response rates: 79% and 86% respectively). The training program for personnel (intervention) was organized between the two studies. It started with a one-hour lecture on postoperative pain and pain treatment in children, and the lecture was followed by two weeks of bedside teaching. The overall standard of pain treatment in the hospital was good. Most of the children had no pain or only mild pain on discharge (93% before the intervention and 90% after the intervention). The intervention had no effect on the likelihood of children receiving pain medication. Noticeable changes occurred in the selection of pain medicines and dosage forms, and in the increased number of home care instructions provided for parents. We conclude that the training program for both professional groups (doctors and nurses) can be beneficial in changing the treatment practice (especially the use of medicines and dosage forms). Such training programs also make it possible to emphasized the importance of proper instructions for home care and thus to improve the quality of information provided for parents.