Anti-angiogenic mechanisms and serotonergic dysfunction in the Rgs2 knockout model for the study of psycho-obstetric risk.

Psychiatric and obstetric diseases are growing threats to public health and share high rates of co-morbidity. G protein-coupled receptor signaling (e.g., vasopressin, serotonin) may be a convergent psycho-obstetric risk mechanism. Regulator of G Protein Signaling 2 (RGS2) mutations increase risk for both the gestational disease preeclampsia and for depression. We previously found preeclampsia-like, anti-angiogenic obstetric phenotypes with reduced placental Rgs2 expression in mice. Here, we extend this to test whether conserved cerebrovascular and serotonergic mechanisms are also associated with risk for neurobiological phenotypes in the Rgs2 KO mouse. Rgs2 KO exhibited anxiety-, depression-, and hedonic-like behaviors. Cortical vascular density and vessel length decreased in Rgs2 KO; cortical and white matter thickness and cell densities were unchanged. In Rgs2 KO, serotonergic gene expression was sex-specifically changed (e.g., cortical Htr2a, Maoa increased in females but all serotonin targets unchanged or decreased in males); redox-related expression increased in paraventricular nucleus and aorta; and angiogenic gene expression was changed in male but not female cortex. Whole-cell recordings from dorsal raphe serotonin neurons revealed altered 5-HT1A receptor-dependent inhibitory postsynaptic currents (5-HT1A-IPSCs) in female but not male KO neurons. Additionally, serotonin transporter blockade by the SSRI sertraline increased the amplitude and time-to-peak of 5-HT1A-IPSCs in KO neurons to a greater extent than in WT neurons in females only. These results demonstrate behavioral, cerebrovascular, and sertraline hypersensitivity phenotypes in Rgs2 KOs, some of which are sex-specific. Disruptions may be driven by vascular and cell stress mechanisms linking the shared pathogenesis of psychiatric and obstetric disease to reveal future targets.

Spontaneous regression of choroidal metastasis from renal cell carcinoma.

Purpose: To report a case of an elderly man who presented with a choroidal metastasis from renal cell carcinoma that spontaneously regressed prior to any local or systemic treatment. Observations: An 82-year-old man without a history of metastatic cancer was referred to the ocular oncology service for evaluation of a newly noted amelanotic choroidal lesion. Examination and imaging findings were concerning for choroidal metastasis. Systemic workup revealed previously undiagnosed widely metastatic renal cell carcinoma. The lesion spontaneously regressed prior to the initiation of any treatment for his tumor. Conclusions and importance: This is a unique case of choroidal metastases from renal cell carcinoma that spontaneously regressed prior to medical or surgical treatment of the primary tumor.

Outcomes following elective cerclage versus ultrasound surveillance in women with one prior preterm event.

OBJECTIVE: Preterm birth, defined as delivery before 37 weeks' gestation, is a major obstetric challenge and is associated with serious long-term complications in those infants that survive. Preventative management includes cervical cerclage, either as an elective procedure or performed following transvaginal ultrasound surveillance and shortening of the cervix (≤25 mm). Significant questions remain regarding the optimal management, target population and technique. Therefore, this study aimed to assess differences in risk factors and pregnancy outcomes for women who received an elective cerclage versus ultrasound surveillance, following one prior premature event (spontaneous preterm birth/second trimester loss). STUDY DESIGN: Women were retrospectively identified from St Thomas's Hospital Preterm Birth Clinical Network Database. Women who had one prior premature event (between 14+0 and 36+6 weeks' gestation) were included and they were separated into those that an elective cerclage and those who underwent ultrasound surveillance to assess differences in demographics, pregnancy risk factors and preterm birth outcomes. We excluded women who received other preventative therapies. We also separately analysed those women who required an ultrasound-indicated cerclage, comparing the differences between women that delivered preterm and term. RESULTS: We collected data from 1077 women who had a prior preterm event. 66 women received an elective cerclage. 11.4% of women who had ultrasound surveillance received an ultrasound indicated cerclage. Women with a prior history of mid-trimester loss, instead of preterm birth, were more likely to receive an elective cerclage. The mean gestational age of delivery was similar between those women who received an elective cerclage and those who had ultrasound surveillance with and without an ultrasound-indicated cerclage (38+1 vs 37+1), however, preterm birth rates <37 weeks' were twice as high in this ultrasound group (OR 2.3 [1.1-4.5], p = 0.02). In those women that do require an ultrasound-indicated cerclage, 50.4% deliver preterm. CONCLUSIONS: In conclusion, this study shows that in women with one prior preterm event, both history-indicated cerclage and ultrasound surveillance are appropriate management options. The majority of women undergoing ultrasound surveillance did not require a cerclage and so avoided the potential perioperative complications of cerclage insertion. However, those that did require an ultrasound-indicated cerclage were at high risk of preterm birth so should be followed up closely to enable adequate preterm birth preparation. Further prospective studies comparing history indicated cerclage and US surveillance in women with one prior preterm event are necessary.

Neonatal outcomes of foetal micrognathia: An 11-year review.

AIM: To identify antenatal features associated with foetal micrognathia that can predict a challenging postnatal management, including difficult airway at delivery, feeding problems and impaired neurological outcomes. METHODS: Single-centre retrospective observational study. Data for antenatally diagnosed cases of micrognathia over 11 years were obtained and analysed. RESULTS: A total of 38 cases were identified, 20 were live births. Of the 16 inborn infants, all had associated congenital anomalies: 14 were diagnosed antenatally, two postnatally. Six of the 16 infants had difficult intubation at birth and three required a tracheostomy. Three died in the neonatal period. The risk of requiring respiratory support at discharge or death was increased if any anomaly was diagnosed antenatally (p = 0.05). There were no differences in respiratory or gastrointestinal morbidities for infants where polyhydramnios was detected antenatally. Of the 13 survivors, two were orally fed, five required a gastrostomy and six were fed by nasogastric/nasojejunal tube. Ten infants were followed up after discharge and seven had normal neurological outcomes. CONCLUSION: There remains no predictive tool available antenatally to anticipate neonatal outcomes. Our associated mortality rate was 64%. Foetal micrognathia rarely occurs in isolation and each case should be referred to a specialist centre for optimal counselling and careful planning.

Fertility Preserving Surgery Outcomes for Ovarian Malignancy: Data from a Tertiary Cancer Centre in Central London.

Fertility Sparing Surgery (FSS) appears to be a safe means of treating early-stage ovarian cancer based on relatively limited evidence. However, there is currently insufficient evidence to aid women in counselling about their potential fertility outcomes. The aim of this study was to assess the reproductive outcomes and prognosis of women who have undergone FSS for ovarian malignancy. Between 1 June 2008 and 1 June 2018, a retrospective review of a clinical database was conducted to identify all consecutive patients who underwent FSS in a central London gynaecological oncology centre. All patients with a histological diagnosis of ovarian malignancy (excluding borderline ovarian tumours) were eligible. All identified patients were then prospectively called into a follow up and asked to complete a questionnaire about their fertility outcomes. A total of 47 women underwent FSS; 36 were included in this study. The mean age was 30.3 years (95% Confidence Interval [CI]: 27.6 to 33.0 years). During the study period, 17/36 (47.2%) of the women had attempted to conceive following surgery, with a successful live birth rate of 52.9% (9/17). The mean time of recurrence was 125.3 months (95% CI: 106.5−144.1 months). The mean time to death was 139.5 months (95% CI: 124.3−154.8). The cancer grade, tumour stage and use of Assisted Reproductive Technology (ART) were the main factors significantly associated with the risk of recurrence and death. In conclusion, this study suggests that a large proportion of women will not attempt to conceive following FSS. For those who do attempt to conceive, the likelihood of achieving a live birth is high. However, careful counselling about the higher risk of recurrence and worse survival for women with high grade cancer, disease Stage > IA and potentially those who undergo ART is essential before contemplating FFS.

Integrating terrestrial laser scanning with functional-structural plant models to investigate ecological and evolutionary processes of forest communities.

BACKGROUND: Woody plants (trees and shrubs) play an important role in terrestrial ecosystems, but their size and longevity make them difficult subjects for traditional experiments. In the last 20 years functional-structural plant models (FSPMs) have evolved: they consider the interplay between plant modular structure, the immediate environment and internal functioning. However, computational constraints and data deficiency have long been limiting factors in a broader application of FSPMs, particularly at the scale of forest communities. Recently, terrestrial laser scanning (TLS), has emerged as an invaluable tool for capturing the 3-D structure of forest communities, thus opening up exciting opportunities to explore and predict forest dynamics with FSPMs. SCOPE: The potential synergies between TLS-derived data and FSPMs have yet to be fully explored. Here, we summarize recent developments in FSPM and TLS research, with a specific focus on woody plants. We then evaluate the emerging opportunities for applying FSPMs in an ecological and evolutionary context, in light of TLS-derived data, with particular consideration of the challenges posed by scaling up from individual trees to whole forests. Finally, we propose guidelines for incorporating TLS data into the FSPM workflow to encourage overlap of practice amongst researchers. CONCLUSIONS: We conclude that TLS is a feasible tool to help shift FSPMs from an individual-level modelling technique to a community-level one. The ability to scan multiple trees, of multiple species, in a short amount of time, is paramount to gathering the detailed structural information required for parameterizing FSPMs for forest communities. Conventional techniques, such as repeated manual forest surveys, have their limitations in explaining the driving mechanisms behind observed patterns in 3-D forest structure and dynamics. Therefore, other techniques are valuable to explore how forests might respond to environmental change. A robust synthesis between TLS and FSPMs provides the opportunity to virtually explore the spatial and temporal dynamics of forest communities.

A Unique Case of Incomplete Bifid Ureter and Associated Arterial Variations.

Introduction. Urogenital and vascular anomalies, including a left duplex kidney and a left aberrant renal artery that gave rise to the left ovarian artery, were observed in a 77-year-old female cadaver during a routine dissection. Description. A left aberrant renal artery, which gave rise to the left ovarian artery, was observed originating from the aorta 4 cm below the left renal artery. Two independent contributions to a bifid ureter were found originating from the hilum of the left kidney. These two contributions descended 12.4 cm and 10.6 cm, respectively, posterior to the left aberrant renal artery and lateral to the left ovarian artery before uniting anterior to the psoas major muscle to descend 12.7 cm to the bladder. Significance. While the duplex kidney is a relatively common congenital anomaly that can be asymptomatic, it can also potentially be associated with compression of renal vasculature or the ureter. Ureteral compression can then result in several pathologies including reflux, urinary tract infection (UTI), ureteropelvic junction obstruction, or hydronephrosis. Compression of renal and ovarian vasculature can result in altered blood flow to the kidney and ovary, potentially causing fibrosis, atrophy, or organ failure. Current imaging techniques alone are insufficient for correct diagnostics of such complications, and they must be supplemented with a thorough understanding of the respective anatomical variations.

Voluntourism.

A rise in international medical volunteering (IMV) poses complex issues for organizations, clinicians, and trainees to navigate. This article explores ethical implications of IMV, such as scope of practice, continuity of care, and erosion of local health systems, and offers a personal perspective from a related field.

Hospitals' Obligations to Address Social Determinants of Health.

Federal health care reform has expanded medical insurance to millions of people, altering the role that hospitals play in improving community health. However, current federal and state community benefit policy is an ineffective tool for ensuring that hospitals address the social determinants of health afflicting their communities. Policy shifts and other incentives that promote improved population health outcomes can encourage health care organizations to do the same.

Are Current Tort Liability Doctrines Adequate for Addressing Injury Caused by AI?

As capabilities of predictive algorithms improve, machine learning will become an important element of physician practice and patient care. Implementation of artificial intelligence (AI) raises complex legal questions regarding health care professionals' and technology manufacturers' liability, particularly if they cannot explain recommendations generated by AI technology. The limited literature on liability for innovation provides opportunities to consider possible implications of AI for medical malpractice and products liability and new legal solutions for addressing liability issues surrounding "black-box" medicine.

Aerosol-Assisted Chemical Vapor Deposition of ZnS from Thioureide Single Source Precursors.

A family of 12 zinc(II) thoureide complexes, of the general form [{L}ZnMe], [{L}Zn{N(SiMe3)2}], and [{L}2Zn], have been synthesized by direct reaction of the thiourea pro-ligands iPrN(H)CS(NMe2) H[L1], CyN(H)CS(NMe2) H[L3], tBuN(H)CS(NMe2) H[L2], and MesN(H)CS(NMe2) H[L4] with either ZnMe2 (1:1) or Zn{N(SiMe3)2}2 (1:1 and 2:1) and characterized by elemental analysis, NMR spectroscopy, and thermogravimetric analysis (TGA). The molecular structures of complexes [{L1}ZnMe]2 (1), [{L2}ZnMe]2] (2), [{L3}ZnMe]∞ (3), [{L4}ZnMe]2] (4), [{L1}Zn{N(SiMe3)2}]2 (5), [{L2}Zn{N(SiMe3)2}]2 (6), [{L3}Zn{N(SiMe3)2}]2] (7), [{L4}Zn{N(SiMe3)2}]2] (8), [{L1}2Zn]2 (9), and [{L4}2Zn]2 (12) have been unambiguously determined using single crystal X-ray diffraction studies. Thermogravimetric analysis has been used to assess the viability of complexes 1-12 as single source precursors for the formation of ZnS. On the basis of TGA data compound 9 was investigated for its utility as a single source precursor to deposit ZnS films on silica-coated glass and crystalline silicon substrates at 150, 200, 250, and 300 °C using an aerosol assisted chemical vapor deposition (AACVD) method. The resultant films were confirmed to be hexagonal-ZnS by Raman spectroscopy and PXRD, and the surface morphologies were examined by SEM and AFM analysis. Thin films deposited from (9) at 250 and 300 °C were found to be comprised of more densely packed and more highly crystalline ZnS than films deposited at lower temperatures. The electronic properties of the ZnS thin films were deduced by UV-Vis spectroscopy to be very similar and displayed absorption behavior and band gap (Eg = 3.711-3.772 eV) values between those expected for bulk cubic-ZnS (Eg = 3.54 eV) and hexagonal-ZnS (Eg = 3.91 eV).

Transformation of Biopharmaceutical Classification System Class I and III Drugs Into Ionic Liquids and Lipophilic Salts for Enhanced Developability Using Lipid Formulations.

Higher lipid solubility of lipophilic salt forms creates new product development opportunities for high-dose liquid-filled capsules. The purpose of this study is to determine if lipophilic salts of Biopharmaceutical Classification System (BCS) Class I amlodipine and BCS Class III fexofenadine, ranitidine, and metformin were better lipid formulation candidates than existing commercial salts. Lipophilic salts were prepared from lipophilic anions and commercial HCl or besylate salt forms, as verified by 1H-NMR. Thermal properties were assessed by differential scanning calorimetry and hot-stage microscopy. X-ray diffraction and polarized light microscopy were used to confirm the salt's physical form. All lipophilic salt forms were substantially more lipid-soluble (typically >10-fold) when compared to commercial salts. For example, amlodipine concentrations in lipidic excipients were limited to <5-10 mg/g when using the besylate salt but could be increased to >100 mg/g when using the docusate salt. Higher lipid solubility of the lipophilic salts of each drug translated to higher drug loadings in lipid formulations. In vitro tests showed that lipophilic salts solubilized in a lipid formulation resulted in dispersion behavior that was at least as rapid as the dissolution rates of conventional salts. This study confirmed the applicability of forming lipophilic salts of BCS I and III drugs to promote the utility of lipid-based delivery systems.

Synthesis and structural characterisation of transition metal fluoride sulfates.

Eleven first row transition metal fluoride sulfates synthesised in hydrofluorothermal conditions have been structurally characterised by single crystal X-ray diffraction and exhibit a wide variety of structural motifs. The polyionic structures containing Ti, V, Mn and Fe vary from discrete polyhedral units in Na4TiF4(SO4)2 and [N2C10H12] TiF4SO4, through one dimensional chains in (K2FeF3SO4, Li3FeF2(SO4)2·H2O, Li1.87Ti1.13O0.39F1.61(SO4)2, [N2C10H12]TiF2(SO4)2, [N2C6H16]Fe(SO4)2F and [N2C6H16]V(SO4)2F), and to two dimensional layers in ([N2C6H16](2+)Mn2F2(SO4)2, Na2VF3SO4 and Na3CrF2(SO4)2).