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Selective estrogen receptor modulators (SERMs) act as estrogen receptor (ER) agonists or antagonists in a tissue-specific manner. ERs exert effects via nuclear actions but can also utilize membrane-initiated signaling pathways. To determine if membrane-initiated ERα (mERα) signaling affects SERM action in a tissue-specific manner, C451A mice, lacking mERα signaling due to a mutation at palmitoylation site C451, were treated with Lasofoxifene (Las), Bazedoxifene (Bza), or estradiol (E2), and various tissues were evaluated. Las and Bza treatment increased uterine weight to a similar extent in C451A and control mice, demonstrating mERα-independent uterine SERM effects, while the E2 effect on the uterus was predominantly mERα-dependent. Las and Bza treatment increased both trabecular and cortical bone mass in controls to a similar degree as E2, while both SERM and E2 treatment effects were absent in C451A mice. This demonstrates that SERM effects, similar to E2 effects, in the skeleton are mERα-dependent. Both Las and E2 treatment decreased thymus weight in controls, while neither treatment affected the thymus in C451A mice, demonstrating mERα-dependent SERM and E2 effects in this tissue. Interestingly, both SERM and E2 treatments decreased the total body fat percent in C451A mice, demonstrating the ability of these treatments to affect fat tissue in the absence of functional mERα signaling. In conclusion, mERα signaling can modulate SERM responses in a tissue-specific manner. This novel knowledge increases the understanding of the mechanisms behind SERM effects and may thereby facilitate the development of new improved SERMs.

Background/Aim The mandible makes up a substantial part of the lower face, and is susceptible to injury. Even in helmeted cyclists, accidents may lead to fractures of the mandible because conventional helmets provide little protection to the lower part of the face. In addition, some studies indicate that helmets may lead to an increased risk of mandibular fractures. Thus, the aim of this study was to examine the anatomic distribution of mandibular fractures in injured cyclists and to assess if helmet use influenced the fracture locations. Material and Methods Data from a Norwegian Level 1 trauma center were collected in the Oslo University Hospital Trauma Registry over a 12-year period. Of 1543 injured cyclists, the electronic patient charts of 62 cyclists with fractures of the mandible were retrospectively evaluated in detail. Demographic data, helmet use, and fracture type were assessed. Results Sixty-two patients (4%) had fractures of the mandible, and women had an increased risk (OR 2.49, 95% CI 1.49–4.16, p

Purpose Identifying factors causing Molar-Incisor Hypomineralization (MIH) is an ongoing challenge. Preterm infants, routinely treated with antibiotics in cases of suspected sepsis, are more commonly affected by dental developmental defects. This study aimed to investigate the effects of gentamycin and ampicillin on the developing enamel in neonatal CD-1 mice in vivo. Methods Neonatal mice were randomized into a study (n = 36) and a control (n = 35) group. Antibiotics were injected intravenously for 4 days. All mice were sacrificed after 15–18 days. Micro-CT was used to analyse the mineral density (MD) of the enamel and the proportion of the enamel object volume (vol%) in first molars and incisors. Results We demonstrated a significantly lower vol% enamel in the maxillary (30.9% vs. 32.7%; p = 0.004) and mandibular (32.5% vs. 34.6%; p = 0.015) molars in the study group than in the controls. The incisors were divided into segments upon analysis. We demonstrated both lower vol% and lower MD of the enamel in most segments in treated individuals compared to controls (p Conclusion The reduced MD and vol% in the molars and incisors are likely to have been caused by the antibiotics given during tooth development. The presented analysis of teeth in neonatal mice with micro-CT could be a valid model for further research on dental developmental defects.

During the last decade, uterus transplantation has evolved as the first treatment for absolute uterine factor infertility, caused by absence of a functional uterus. Current challenges in the area of uterus transplantation are organ shortage and side effects of immunosuppression. These hurdles may be solved with novel tissue engineering technologies to produce a uterus from stem cells. For example, the development of patient-specific grafts using a biomaterial together with the patient’s own cells might be utilized for a partial uterus repair therapy or a whole bioengineered uterus might be developed to replace an allogeneic graft in a uterus transplantation setting. During recent years, uterus bioengineering strategies with scaffolds based on decellularized tissue have been particularly assessed. Decellularization protocols were established for both small and large animal models, including the human uterus. Promising in vivo results using such scaffolds to repair a partially injured uterus showed restoration of fertility in rodent models. Scaffold generation protocols and recellularization methodologies including various cell sources are currently being optimized and translated to more clinically relevant injury models in large animals. This review provides a summary of the progress made to date, based on use of decellularized uterine tissue for uterus repair.

Inflammation has a significant effect on bone remodeling and can result in bone loss via increased stimulation of osteoclasts. Activated immunoglobulins, especially autoantibodies, can increase osteoclastogenesis and are associated with pathological bone loss. Whether immunoglobulins and mature B lymphocytes are important for general bone architecture has not been completely determined. Here we demonstrate, using a transgenic mouse model, that reduction of mature B cells and immunoglobulins leads to increased trabecular bone mass compared to wild-type (WT) littermate controls. This bone effect is associated with a decrease in the number of osteoclasts and reduced bone resorption, despite decreased expression of osteoprotegerin. We also demonstrate that the reduction of mature B cells and immunoglobulins do not prevent bone loss caused by estrogen deficiency or arthritis compared to WT littermate controls. In conclusion, the reduction of mature B cells and immunoglobulins results in disturbed regulation of trabecular bone turnover in healthy conditions but is dispensable for pathological bone loss. © 2022 The Authors.

Aim: To report on the management strategies in patients with cancer of unknown primary (CUP) in middle-income countries. Methods: We conceived a survey of 20 items concerning the management of patients with CUP in daily clinical practice. Only participants from lower- and higher-middle-income countries, as per the World Bank Classification, were eligible for this study. Results: The indications for the first-line treatment did not differ between the two economic regions, whereas those for second-line treatment were more prevalent in higher-middle-income countries. The use of targeted therapy based on immunohistochemistry alone was higher in lower-middle-income countries, although the access to CUP classifiers was similar between the two regions. Conclusions: Proper recommendations must ensure that the economic burden is minimized and that other benefits outweigh the limited survival benefit achieved in patients with CUP.

Uterus tissue engineering may dismantle limitations in current uterus transplantation protocols. A uterine biomaterial populated with patient-derived cells could potentially serve as a graft to circumvent complicated surgery of live donors, immunosuppressive medication and rejection episodes. Repeated uterine bioengineering studies on rodents have shown promising results using decellularised scaffolds to restore fertility in a partially impaired uterus and now mandate experiments on larger and more human-like animal models. The aim of the presented studies was therefore to establish adequate protocols for scaffold generation and prepare for future in vivo sheep uterus bioengineering experiments. Three decellularisation protocols were developed using vascular perfusion through the uterine artery of whole sheep uteri obtained from slaughterhouse material. Decellularisation solutions used were based on 0.5% sodium dodecyl sulphate (Protocol 1) or 2% sodium deoxycholate (Protocol 2) or with a sequential perfusion of 2% sodium deoxycholate and 1% Triton X-100 (Protocol 3). The scaffolds were examined by histology, extracellular matrix quantification, evaluation of mechanical properties and the ability to support foetal sheep stem cells after recellularisation. We showed that a sheep uterus can successfully be decellularised while maintaining a high integrity of the extracellular components. Uteri perfused with sodium deoxycholate (Protocol 2) were the most favourable treatment in our study based on quantifications. However, all scaffolds supported stem cells for 2 weeks in vitro and showed no cytotoxicity signs. Cells continued to express markers for proliferation and maintained their undifferentiated phenotype. Hence, this study reports three valuable decellularisation protocols for future in vivo sheep uterus bioengineering experiments.

In spine deformity surgery, iatrogenic neurologic injuries might occur due to the mechanical force applied to the spinal cord from implants, instruments, and bony structures, or due to ischemic changes from vessel ligation during exposure and cord distraction/compression during corrective manoeuvres. Prompt reaction within the reversible phase (reducing of compressive/distractive forces) usually restores functionality of the spinal cord, but if those forces continue to persist, a permanent neurological deficit might be expected. With monitoring of sensory pathways (dorsal column–medial lemniscus) by somatosensory-evoked potentials (SSEPs), such events are detected with a sensitivity of up to 92%, and a specificity of up to 100%. The monitoring of motor pathways by transcranial electric motor-evoked potentials (TceMEPs) has a sensitivity and a specificity of up to 100%, but it requires avoidance of halogenated anaesthetics and neuromuscular blockades. Different modalities of intraoperative neuromonitoring (IONM: SSEP, TceMEP, or combined) can be performed by the neurophysiologist, the technician or the surgeon. Combined SSEP/TceMEP performed by the neurophysiologist in the operating room is the preferable method of IONM, but it might be impractical or unaffordable in many institutions. Still, many spine deformity surgeries worldwide are performed without any type of IONM. Medicolegal aspects of IONM are different worldwide and in many cases some vagueness remains. The type of IONM that a spinal surgeon employs should be reliable, affordable, practical, and recognized by the medicolegal guidelines.Cite this article: EFORT Open Rev 2020;5:9-16. DOI: 10.1302/2058-5241.5.180032

The use of resolution recovery (RR) in bone and myocardial perfusion imaging is becoming increasingly popular in nuclear medicine departments. RR produces reconstructed images that show improved spatial resolution and signal-to-noise ratio compared with conventional single-photon emission computed tomography (SPECT) images.To evaluate the impact of the ordered subset expectation maximization (OSEM) RR modality on preserving noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) for short SPECT acquisition.This prospective study was conducted on 80 patients. Full SPECT acquisition was performed as a standardized protocol, while reduced acquisition was achieved with the Poisson resampling method. Noise, SNR, and CNR were measured for different reconstruction parameters for the same image levels. The impact of surface area and body mass index was also measured for the same reconstruction parameters.The results show significantly higher SNR and CNR for the Evolution for Bone protocol compared to the other two reconstruction protocols for full and reduced SPECT acquisition. With the shortening of the SPECT acquisition, an increase in the value of noise was recorded. SNR and CNR decreased with the reduction in SPECT acquisition.The Evolution for Bone protocol for all three analyzed acquisition protocols had the lowest noise values. The highest SNR and CNR were recorded in the Evolution for Bone protocol for the three acquisition protocols and SPECT acquisition time can be reduced from 20 to 10 min for bone SPECT.

Supplemental material, sj-docx-1-tej-10.1177_20417314221118858 for Mesenchymal stem cells establish a pro-regenerative immune milieu after decellularized rat uterus tissue transplantation by Edina Sehic, Emy Thorén, Ingigerdur Gudmundsdottir, Mihai Oltean, Mats Brännström and Mats Hellström in Journal of Tissue Engineering

The dwarf succulent genus Lithops is endemic to Southern Africa and of considerable conservation concern. Species delimitation is often problematic and based mainly on leaf morphology, which is strongly associated with habitat. Relationships between taxa and populations in Namibia were studied with amplified fragment length polymorphisms using 44 wild Lithops populations representing 15 species and 23 taxa. Four primer pairs produced 92 polymorphic bands in the 223 samples. Expected heterozygosity (He) within taxa ranged from 0.086 to 0.450. Genetic and geographic distances were correlated according to a Mantel test. Analysis of molecular variance showed only 23% variation among the 15 investigated species. Genetic differentiation and structuring were investigated with a principal coordinate analysis, a neighbour-joining and a Bayesian phylogeny, a Bayesian clustering analysis and a discriminant analysis of principal components. In all five analyses, L. optica and L. herrei, which differ only in flower colour, clustered closely together and are here combined under L. optica. The morphologically similar species L. amicorum and L. karasmontana clustered together. Lithops amicorum is therefore reduced to subspecific level: L. karasmontana subsp. amicorum, comb. nov. Subspecific taxa overlapped to a large extent except in L. karasmontana where 13% of the variability resided among subspecies, whereas the nominal subspecies differed from subsp. bella and subsp. eberlanzii; the latter two could not be separated and are here combined under L. karasmontana subsp. bella.