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A series of 230 patients was studied with a view to the effect of the time interval between cone biopsy of the cervix and hysterectomy on the postoperative febrile course and on the incidence of severe complications, such as abscess and/or haematoma in the true pelvis or in the abdominal wound. Fever as well as severe complications were found to be most common in patients treated by hysterectomy 4-14 days after cone biopsy. The causes are discussed. It is concluded that cone biopsy and hysterectomy should be carried out at the same time, with frozen section microscopy of the biopsy. Otherwise, the hysterectomy should be deferred until 5 or 6 weeks after the cone biopsy. [ABSTRACT FROM AUTHOR]

Chemical modification of messenger RNA (mRNA) has paved the way for advancing mRNA-based therapeutics. The intricate process of mRNA translation in eukaryotes is orchestrated by numerous proteins involved in complex interaction networks. Many of them bind specifically to a unique structure at the mRNA 5'-end, called 5'-cap. Depending on the 5'-terminal sequence and its methylation pattern, different proteins may be involved in the translation initiation and regulation, but a deeper understanding of these mechanisms requires specialized molecular tools to identify natural binders of mRNA 5'-end variants. Here, a series of 8 new synthetic 5'-cap analogs that allow the preparation of RNA molecules with photoreactive tags using a standard in vitro transcription reaction are reported. Two photoreactive tags and four different modification sites are selected to minimize potential interference with cap-protein contacts and to provide complementary properties regarding crosslinking chemistry and molecular interactions. The tailored modification strategy allows for the generation of specific crosslinks with model cap-binding proteins, such as eIF4E and Dcp2. The usefulness of the photoreactive cap analogs is also demonstrated for identifying the cap-binding subunit in a multi-protein complex, which makes them perfect candidates for further development of photoaffinity labeling probes to study more complex mRNA-related processes., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The coronavirus disease 2019 pandemic resulted in the underutilization of inpatient beds at our satellite location. A lack of clarity and standardized admission criteria for the satellite led to frequent transfers to the main campus, resulting in patients traveling larger distances to receive inpatient care. We sought to optimize inpatient resource use at the satellite campus and keep patients "closer to home" by admitting eligible patients to that inpatient unit (LA4). Our aim was to increase bed capacity use at the satellite from 45% to 70% within 10 months. Our process measure was to increase the proportion of patients needing hospitalization who presented to the satellite emergency department (ED) and were then admitted to LA4 from 76% to 85%., Methods: A multidisciplinary team used quality improvement methods to optimize bed capacity use. Interventions included (1) the revision and dissemination of satellite admission guidelines, (2) steps to create shared understanding of appropriate satellite admissions between ED and inpatient providers, (3) directed provider feedback on preventable main campus admissions, and (4) consistent patient and family messaging about the potential for transfer. Data were collected via chart review. Annotated run charts were used to assess the impact of interventions over time., Results: Average LA4 bed capacity use increased from 45% to 69%, which was sustained for 1 year. The average percentage of patients admitted from the satellite ED to LA4 increased from 76% to 84%., Conclusions: We improved bed capacity use at our satellite campus through transparent admission criteria and shared mental models of patient care needs between ED and inpatient providers., (Copyright © 2024 by the American Academy of Pediatrics.)

Introduction: There is sufficient scientific literature that demonstrates favorable outcomes using the minimally invasive technique of middle meningeal artery embolization (MMAE) for the treatment of chronic subdural hematomas (cSDH). The authors evaluate the outcomes of 35 consecutive patients treated with MMAE, both with and without adjuvant surgical drainage (ASD), in an attempt to identify variables that may affect the outcome of patients treated with MMAE for cSDH., Methods: A multivariate retrospective analysis was performed on patients who received MMAE for cSDH, including age, size of cSDH, ASD, presence of unilateral or bilateral collections, and use of anticoagulants., Results: Twenty patients underwent MMAE with planned ASD, while 15 patients had MMAE only; these groups had an average cSDH size reduction (measured at its greatest width) of 74% and 69% of cSDH, respectively. Of the 15 patients who were initially treated only with MMAE, three (20%) required a rescue craniotomy. Twenty patients (57%) who had initially presented while receiving oral anticoagulants had an average of 71% size reduction with ASD compared to 74% reduction in those without ASD. Patients not using anticoagulants had an 84% and 78% average reduction in size, respectively. Twelve patients presented with bilateral cSDH; patients who received ASD had an average size reduction of 58%; those without ASD had 63%. Patients with unilateral cSDH had 85% and 83% reduction in size, respectively., Conclusion: Middle meningeal artery embolization, with or without ASD, can be a useful alternative or adjunct to standard surgical treatment for cSDH. Our study found that only three of 35 patients (9%) treated with this method required any further surgical intervention. No patient who received ASD had a recurrence of their cSDH. Further investigation, including prospective randomized studies, would be useful to better identify which patients can benefit and variables that impact the outcome of patients undergoing MMAE., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Palumbo et al.)

This work, based on in vivo and in vitro measurements, as well as in silico simulations, provides a consistent analysis of diffusion of polydisperse nanoparticles in the cytoplasm of living cells. Using the example of fluorescence correlation spectroscopy (FCS), we show the effect of polydispersity of probes on the experimental results. Although individual probes undergo normal diffusion, in the ensemble of probes, an effective broadening of the distribution of diffusion times occurs-similar to anomalous diffusion. We introduced fluorescently labeled dextrans into the cytoplasm of HeLa cells and found that cytoplasmic hydrodynamic drag, exponentially dependent on probe size, extraordinarily broadens the distribution of diffusion times across the focal volume. As a result, the in vivo FCS data were effectively fitted with the anomalous subdiffusion model while for a monodisperse probe the normal diffusion model was most suitable. Diffusion time obtained from the anomalous diffusion model corresponds to a probe whose size is determined by the weight-average molecular weight of the polymer. The apparent anomaly exponent decreases with increasing polydispersity of the probes. Our results and methodology can be applied in intracellular studies of the mobility of nanoparticles, polymers, or oligomerizing proteins.

Serotonin(6) (5-HT(6)) receptors are almost exclusively located in the central nervous system. High expression in the hippocampus, nucleus accumbens and striatum is consistent with a potential role in cognition and psychosis. The availability of potent, selective and brain-penetrating 5-HT(6) antagonists such as RO4368554 allows further characterization of the role of the 5-HT(6) receptor in these processes. Herein, we tested RO4368554 in several cognition tasks, as well as sensorimotor gating tests. Using scopolamine-impaired and unimpaired adult male rats, RO4368554 was given in novel object discrimination, social recognition, social discrimination, Morris water maze, passive avoidance and autoshaping procedures. RO4368554 reversed the effects of scopolamine in novel object discrimination (active doses in mg/kg, i.p., 3, 10), social recognition (3, 10), social discrimination (1, 3, 10) and passive avoidance (10, 30 i.p. and 100 p.o.) tasks. In unimpaired rats, RO4368554 enhanced object discrimination (3, 10; 4-h forgetting interval) and autoshaping learning (3), but was inactive in a water maze task (doses tested: 1-10 mg/kg, i.p.). In tests sensitive to antipsychotics, RO4368554 did not reverse sensorimotor gating deficits induced by the psychostimulants dizocilpine and amphetamine (doses tested: 1-30 mg/kg, i.p.) or neonatal lesion of the ventral hippocampus (1-10 mg/kg, i.p.). In conclusion, RO4368554 enhanced learning and memory processes in unimpaired and scopolamine-impaired rats, supporting the notion that the cognitive enhancing effects of 5-HT(6) receptor antagonists involve modulation of cholinergic neurotransmission.

The 5-HT2C receptor is one of three closely related receptor subtypes in the 5-HT2 receptor family. 5-HT2A and 5-HT2B selective antagonists have been described. However, no 5-HT2C selective antagonists have yet been disclosed. As part of an effort to further explore the function of 5-HT2C receptors, we have developed a selective 5-HT2C receptor antagonist, RS-102221 (a benzenesulfonamide of 8-[5-(5-amino-2,4-dimethoxyphenyl) 5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione). This compound exhibited nanomolar affinity for human (pKi = 8.4) and rat (pKi = 8.5) 5-HT2C receptors. The compound also demonstrated nearly 100-fold selectivity for the 5-HT2C receptor as compared to the 5-HT2A and 5-HT2B receptors. RS-102221 acted as an antagonist in a cell-based microphysiometry functional assay (pA2 = 8.1) and had no detectable intrinsic efficacy. Consistent with its action as a 5-HT2C receptor antagonist, daily dosing with RS-102221 (2 mg/kg intraperitoneal) increased food-intake and weight-gain in rats. Surprisingly, RS-102221 failed to reverse the hypolocomotion induced by the 5-HT2 receptor agonist 1-(3-chlorophenyl)piperazine (m-CPP). It is concluded that RS-102221 is the first selective, high affinity 5-HT2C receptor antagonist to be described.

Dogs were submitted to one of three hemorrhagic shock procedures: normovolemic shock, oligemic hypotension or posthemorrhagic hypotension. 13 animals fulfilled well-filled criteria of irreversible hemorrhagic shock, based on mortality, take-up volume and metabolic changes. Lung function was measured at regular intervals. Lungs were fixed by infusion fixation. The macroscopial aspect of the lungs was not different from that of six control dogs which were anesthetized for the same period. Minor microscopical changes were found, but the only histological parameter which was significantly different from the controls was accumulation of granulocytes. Gas exchange remained normal, ventilation was increased with an enlarged dead space and veno-arterial shunting was reduced. Pulmonary vascular resistance was not different from the control group.

Cardioplegia according to Bretschneider is able to protect the myocardium during long periods of cardiac arrest and a quiet relaxed heart has in many cases of congenital heart disease been of great surgical advantage. In the last 100 consecutive aortic valve replacements in cardioplegic arrest we have lost 6 patients and none of the deaths seems to be related to the method. In our hands it has been superior to coronary perfusion.