Evidence For Other Types Research Articles

Decision-Making for Adolescents with Gender Dysphoria.

Legislation banning gender-affirming medical care (GAMC) for minors is inconsistent with the Consensus Recommendations for Pediatric Decision-Making (Salter et al. 2023). Gender dysphoria is a medical condition, and GAMC promotes adolescents' health interests. The evidence for GAMC is comparable to the evidence for other types of pediatric medical care. Parents are permitted to consent for similar risks in the treatment of other conditions. Evaluation of the potential benefits, risks, and treatment alternatives is contingent on individual patients' clinical conditions and adolescents' and their parents' values and preferences. Such decisions are within the scope of parental discretion and should be made through shared decision-making with health-care providers. Parents' declining GAMC does not inherently create a significant risk of serious imminent harm required to justify state intervention. Usurping parental discretion for GAMC is unjust: it treats this medical care differently than other comparable types of medical care without sufficient justification.

EXTRA-ARTICULAR KNEE LIGAMENT RECONSTRUCTIONS USING LIGAMENT AUGMENTATION AND RECONSTRUCTION SYSTEM (LARS) SYNTHETIC GRAFTS IN ELITE ATHLETES

IntroductionTo determine if elite athletes can return to professional sport after MCL or posterolateral (PLC) reconstruction using LARS ligaments. The secondary aims are to demonstrate the safety and efficacy of LARS by reporting sport longevity, subsequent surgeries, and complications.MethodsA retrospective review of all extra-articular knee ligament reconstructions, utilising a LARS synthetic ligament, by 3 sports knee surgeons between 2013 and 2020 was undertaken. All elite athletes aged over 16 years and a minimum of 2 years post reconstruction were included. No LARS were used for ACL reconstructions, and they were excluded if a LARS ligament was used for a PCL reconstruction. Return to play (RTP) was defined as competing at professional level or national/ international level in amateur sport.ResultsSixty-four (84.2%) MCL reconstructions and 12 (15.8%) PLC reconstructions were included. 52 (68.4%) underwent concomitant autograft cruciate(s) reconstruction including 6 (7.8%) bicruciate reconstructions. The mean age was 25.1 years (SD +/− 4.50). 35 (46.1%) were footballers and 35 (46.1%) were rugby players. Sixty-seven athletes (88.2%) returned to elite sport, 7 (9.2%) did not RTP and RTP status was unknown for 2 (2.6%) (Figure 1). 65 out of 67 (97.0%) RTP at the same/higher Tegner level. 56 (83.6%) and 20 (57.1%) were still playing at 2- and 5-years post-surgery Six (7.9%) players required further surgery due to irritation from the metal fixation implants. One had an inflammation adjacent to the synthetic material at the femoral end and the other cases involved the tibial staples. All six cases were able to RTP. One athlete, following bicruciate /MCL surgery had the LARS removed due to laxity. There was one MCL re-rupture, sustained while jumping, 4 years after returning to football.ConclusionsUtilising LARS in extra-articular knee ligament reconstructions allows 88.2% of athletes with a variety of knee ligament injuries to return to elite sport. The results compare well regarding RTP, complication, and revision rates with the published evidence for other types of MCL and PLC grafts. This, coupled with 57% of athletes still playing 5 years post-surgery suggests the LARS is safe and effective in these cases.For any figures or tables, please contact authors directly.

Maternal medically diagnosed infection and antibiotic prescription during pregnancy and risk of childhood cancer: A population-based cohort study in Taiwan, 2004 to 2015.

While associations between maternal infections during pregnancy and childhood leukemia in offspring have been extensively studied, the evidence for other types of childhood cancers is limited. Additionally, antibiotic exposure during pregnancy could potentially increase the risk of childhood cancers. Our study investigates associations between maternal infections and antibiotic prescriptions during pregnancy and the risk of childhood cancer in Taiwan. We conducted a population-based cohort study using the Taiwan Maternal and Child Health Database (TMCHD), linked with national health and cancer registries. The study included 2 267 186 mother-child pairs, and the median follow-up time was 7.96 years. Cox proportional hazard models were utilized to estimate effects. Maternal infections during pregnancy were associated with a moderate increase in the risk of childhood hepatoblastoma (adjusted hazard ratio [HR] = 1.34; 95% confidence interval [CI]: 0.90-1.98) and a weaker increase in the risk of childhood acute lymphoblastic leukemia (ALL) (adjusted HR = 1.15; 95% CI: 0.99-1.35). Antibiotic prescriptions during pregnancy were also associated with an elevated risk of childhood ALL (adjusted HR = 1.30; 95% CI: 1.04-1.63), particularly with tetracyclines (adjusted HR = 2.15; 95% CI: 1.34-3.45). Several specific antibiotics were also associated with an increased risk of hepatoblastoma and medulloblastoma. Children exposed in utero to antibiotic prescription or both infections and antibiotics during pregnancy were at higher risk of developing ALL. Our findings suggest that there are associations between maternal infections, antibiotic use during pregnancy and the risk of several childhood cancers in addition to ALL and highlight the importance of further research in this area.

Risk of myocardial infarction and ischemic stroke in individuals with first-diagnosed paroxysmal vs. non-paroxysmal atrial fibrillation under anticoagulation.

There is conflicting evidence on whether the type of atrial fibrillation (AF) is associated with risk of cardiovascular events, including acute myocardial infarction (MI) and ischemic stroke. The aim of the present study was to investigate whether the risk of MI and ischemic stroke differs between individuals with first-diagnosed paroxysmal vs. non-paroxysmal AF treated with anticoagulants. De-identified electronic medical records from the TriNetX federated research network were used. Individuals with a new diagnosis of paroxysmal AF who had no evidence of other types of AF in their records were 1:1 propensity score-matched with individuals with non-paroxysmal AF, defined as persistent or chronic AF, who had no evidence of other types of AF in their records. All patients were followed for three years for the outcomes of MI and ischemic stroke. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). In the propensity-matched cohort, among 24 848 well-matched AF individuals [mean age 74.4 ± 10.4; 10 101 (40.6%) female], 410 (1.7%) were diagnosed with acute MI and 875 (3.5%) with ischemic stroke during the three-year follow-up. Individuals with paroxysmal AF had significantly higher risk of acute MI (HR: 1.65, 95%CI: 1.35-2.01) compared to those with non-paroxysmal AF. First diagnosed paroxysmal AF was associated with higher risk of non-ST elevation MI (nSTEMI) (HR: 1.89, 95%CI: 1.44-2.46). No significant association was observed between the type of AF and risk of ischemic stroke (HR: 1.09, 95%CI: 0.95-1.25). Patients with first-diagnosed paroxysmal AF had higher risk of acute MI compared to individuals with non-paroxysmal AF, attributed to the higher risk of nSTEMI among patients with first-diagnosed paroxysmal AF. There was no significant association between type of AF and risk of ischemic stroke.

Introduction, Summary, Questions for the Future

Introduction, Summary, Questions for the Future

Single-Cell Transcriptomic Analysis Reveals Reduction of Cytotoxic NK Cells in a Subset of Newly Diagnosed Multiple Myeloma Patients Impacting Outcome after Daratumumab Therapy

Introduction Anti-CD38 antibody-based therapies in multiple myeloma (MM) rely to a large degree on natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Classically, NK cells are divided into cytotoxic CD56dim NK cells, important for ADCC, and cytokine-producing CD56bright NK cells. Accumulating evidence in other types of cancer suggests that alterations in the balance between CD56dim and CD56bright NK cells is associated with inferior clinical outcome. We hypothesized that changes in NK cell subset composition in the MM microenvironment would impact therapy-responses during NK cell-driven immunotherapies. Here, we used single-cell RNA sequencing and flow cytometry to investigate the heterogeneity of the NK cell compartment in the bone marrow (BM) of newly diagnosed MM (NDMM) patients, and the effects of altered NK cell subset composition on therapy response in patients undergoing first-line daratumumab-containing therapy. Results We performed single-cell RNA sequencing of the BM CD38+ immune cell compartment from 19 NDMM patients. NK cells were identified in silico resulting in a single-cell transcriptomic dataset of 24,664 NK cells. UMAP dimensionality reduction identified 5 transcriptomic distinct NK cell clusters, present in all NDMM patients. Conventional CD56bright and CD56dim NK cells were identified by increased transcription of GZMK or GZMB, respectively. To study the balance of cytotoxic vs cytokine-producing NK cells in MM we compared the relative abundance of cytokine-producing GZMK+CD56bright NK cells vs cytotoxic GZMB+CD56dim NK cells in individual patients in our cohort. The MM BM was characterized by heterogeneity in the ratio of cytotoxic vs cytokine-producing NK cell cluster composition, in which most patients had a predominance of cytotoxic NK cells, while a subset of patients presented with a relative decrease in cytotoxic NK cell clusters (Figure 1A). The reduction in cytotoxic NK cell subsets in this patient subgroup was reflected in an altered overall transcriptome of the total BM NK cell population, with enrichment for inhibitory receptors such as KLRB1 and KLRC1, and a relative loss of activating receptors such as FCGR3A (CD16), NCR3 (NKp30) and CD226 (DNAM-1), and cytotoxic effector genes including NKG7 and GNLY. To define the relative abundance of a reduced cytotoxic NK cell potential in NDMM patients, we performed flow cytometric analyses of 246 NDMM patients from 2 independent clinical cohorts. This revealed a reduced frequency of cytotoxic CD56dim NK cells, defined as < 90% CD56dim NK cells, in 17.9 % of 162 transplant-eligible treatment-naïve NDMM and in 28.6% of 84 treatment-naïve frail or unfit transplant ineligible MM patients. To test whether such relative decrease in cytotoxic NK cells would impact responses to daratumumab, we tested the association of BM NK cell composition with clinical outcome in the context of first-line daratumumab therapy in a cohort of frail NDMM patients ineligible for transplant from the HO143 trial (n=43). NDMM patients with reduced frequencies of BM cytotoxic NK cells presented with significantly shorter progression-free survival (PFS) (Figure 1B, PFS, p = 0.031, log-rank test), while OS was not impacted (p = 0.18, log-rank test). Univariate Cox regression analyses confirmed the correlation between reduced frequencies of CD56dim NK cells in the BM and significantly shorter PFS (hazard ratio (HR) 1.38; 95% confidence interval: 1.057 - 1.803; P = 0.018). Whether reduced frequencies of cytotoxic CD56dim NK cells affect outcome in transplant-eligible patients warrants additional study. Conclusion Here we show that about 20% of NDMM patients have an altered BM NK cell composition with a relative reduction in cytotoxic NK cells. Such altered NK cell composition correlates with significantly shorter PFS following daratumumab-containing therapy in a cohort of frail NDMM patients. Our data suggest that defining BM NK cell composition could stratify patients and identify a subgroup less likely to benefit from therapies driven by NK cell-mediated ADCC. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Immunotherapy in head and neck squamous cell carcinoma: a narrative review.

Objective:Provide a narrative review of the literature describing immunological concepts and novel approaches in the treatment of head and neck squamous cell carcinoma.Background:In 2016, two anti-PD1 antibodies, nivolumab and pembrolizumab, were shown to improve overall survival in patients with recurrent/metastatic HNSCC and were approved by the US Food and Drug Administration (FDA) for use in the second line, cisplatin-resistant setting, although the overall response rates were only about 15%. More recently, pembrolizumab was approved for use in the first-line R/M setting as monotherapy in patients with CPS >1 or in combination with chemotherapy regardless of PD-L1 expression. Interestingly, while response rates with combination therapy were increased compared to pembrolizumab alone, the duration of response was shorter than might be expected. Based on a growing amount of evidence in other types of cancer treated with various combinations of immunotherapy, similar concepts are being studied in HNSCC, both in pre-clinical models and in clinical trials.Methods:A review of the literature was conducted using the Medline-PubMed and ClinicalTrials.gov databases. Main topics were selected for review, including basic immunology background, checkpoint inhibition, neoadjuvant immunotherapy, the combination of immunotherapy with radiation therapy and chemotherapy, intratumoral immunotherapy, and future prospects.Conclusions:There is an ongoing effort, which is supported by an increasing body of evidence, to enhance response rates with combinations of immunotherapy with other immunotherapy agents, targeted small molecules, chemotherapy, radiation therapy, and surgery. The clinician and the scientist should be familiarized with basic immunologic concepts, key findings in recent clinical trials, and current indications for administering immunotherapy.

Epigenetics as a Biomarker for Early-Life Environmental Exposure.

There is interest in evaluating the developmental origins of health and disease (DOHaD) which emphasizes the role of prenatal and early-life environments on non-communicable health outcomes throughout the life course. The ability to rigorously assess and identify early-life risk factors for later health outcomes, including those with childhood onset, in large population samples is often limited due to measurement challenges such as impractical costs associated with prospective studies with a long follow-up duration, short half-lives for some environmental toxicants, and lack of biomarkers that capture inter-individual differences in biologic response to external environments. Epigenomic patterns, and DNA methylation in particular, have emerged as a potential objective biomarker to address some of these study design and exposure measurement challenges. In this article, we summarize the literature to date on epigenetic changes associated with specific prenatal and early-life exposure domains as well as exposure mixtures in human observational studies and their biomarker potential. Additionally, we highlight evidence for other types of epigenetic patterns to serve as exposure biomarkers. Evidence strongly supports epigenomic biomarkers of exposure that are detectable across the lifespan and across a range of exposure domains. Current and future areas of research in this field seek to expand these lines of evidence to other environmental exposures, to determine their specificity, and to develop predictive algorithms and methylation scores that can be used to evaluate early-life risk factors for health outcomes across the life span.

A review of Mohs micrographic surgery for skin cancer. Part 1: Melanoma and rare skin cancers.

Mohs micrographic surgery (MMS) is a precise and effective method commonly used to treat high-risk basal cell carcinoma and squamous cell carcinoma on the head and neck. Although the majority of evidence for MMS relates to keratinocyte cancers, there is published evidence for other types of skin cancer. This review aims to discuss the evidence for using MMS to treat six different types of skin cancer [malignant melanoma, lentigo maligna, dermatofibrosarcoma protuberans, atypical fibroxanthoma (AFX), microcystic adnexal carcinoma and pleomorphic dermal sarcoma (PDS)] particularly in the context of survival rates and cancer recurrence. These cancers were chosen because there was sufficient literature for inclusion and because MMS is most useful when cancers are contiguous, rather than for cancers with marked metastatic potential such as angiosarcoma or Merkel cell carcinoma. We searched MEDLINE, PubMed and Embase using the keywords: 'melanoma', 'mohs micrographic surgery', 'lentigo maligna', 'dermatofibrosarcoma protuberans', 'atypical fibroxanthoma', 'microcystic adnexal carcinoma' and 'pleomorphic dermal sarcoma' along with their appropriate synonyms, to identify the relevant English-language articles from 2000 onwards, given that literature for MMS on nonkeratinocyte cancers is sparse prior to this year. AMSTAR (A MeaSurement Tool to Assess systematic Review) was used to assess the validity of systematic reviews. Further high-quality, multicentre randomized trials are necessary to establish the indications and efficacy of MMS for rarer cancers, particularly for AFX and PDS, for which only limited studies were identified.

Primary Squamous Cell Carcinoma of the Thyroid Coexisting with Tall Cell Variant Papillary Thyroid Carcinoma: Report of Two Cases

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare and aggressive neoplasm of the thyroid, usually presenting with a rapidly growing mass. In order to diagnose a tumor as PSCCT, tumor should entirely consist of cells with squamous differentiation without any evidence of other types of carcinomas. Tall cell variant papillary thyroid carcinoma (TCVPTC) is an aggressive variant of papillary thyroid carcinoma, composed of cells that are two-three times as tall as they are wide. We report two cases of PSCCT coexisting with TCVPTC. In the literature, there are less than 50 cases showing coexistence of PSCCT and TCVPTC. In all these cases, apart from the ones in which pure squamous cell carcinoma (SCC) is seen as a recurrence of TCVPTC, SCC and TCVPTC areas were intermingled. The 2 cases we report here are unique in the way that PSCCT and TCVPTC are seen concurrently in these patients but they are separate tumors, not admixed with each other.

NOX1/4 Inhibitor GKT-137831 Improves Erectile Function in Diabetic Rats by ROS Reduction and Endothelial Nitric Oxide Synthase Reconstitution

BackgroundPrevious studies have shown that oxidative stress contributes to hyperglycemia-induced erectile dysfunction. A preferential direct inhibitor of NOX1 and NOX4, GKT-137831, exhibited a strong anti‑oxidative role via blockade of reactive oxygen species (ROS) generation in endothelial cells, but whether GKT-137831 could improve erectile function was not clear. AimOur study was designed to investigate the effect of NOX1/4 inhibition on improving diabetic erectile dysfunction (ED) in rats. MethodsWe used streptozotocin to induce type 1 diabetes mellitus (DM) in 32 male Sprague Dawley (SD) rats (8 weeks old). Eight weeks later, type 1 diabetes mellitus-induced erectile dysfunction (DMED) in rats was confirmed using an apomorphine test. Our study consisted of 3 groups: (i) nondiabetic control group (n = 8), (ii) DMED + vehicle group (DMED group; n = 8), and (iii) DMED + GKT-137831 group (n = 9); GKT-137831 was given as a once-daily intraperitoneal injection for 4 weeks. Cavernous nerve electrostimulation was used to evaluate erectile function. Western blot, ELISA, immunohistochemistry, and immunofluorescence were used to measure expression of specific proteins, and DHE fluorescent probe was performed to detect ROS level. OutcomesIntracavernous pressure (ICP), nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway, oxidative stress level, inflammatory response, corporal autophagy, and apoptosis were measured. ResultsErectile function in the DMED group was significantly impaired compared to the nondiabetic control group, whereas this impairment was improved with GKT-137831 treatment by 70%. Similarly, endothelial function and overactivated oxidative stress in the corpus cavernosum (CC) of the DMED + GKT-137831 group were improved. The DMED group showed serious inflammatory responses and excessive autophagy, which were inhibited by GKT-137831 treatment in the DMED + GKT-137831 group. Clinical TranslationOur study showed improvement in erectile function with GKT-137831 in a diabetic rat ED model. Strength and LimitationsThis study suggested for the first time that GKT-137831, an NOX1/4 inhibitor undergoing clinical trials, is effective in improving erectile function in rats with type 1 DMED. However, we only investigated GKT-137831 treatment of streptozotocin-induced type 1 diabetic rats, and therapeutic evidence in other types of diabetes is lacking. ConclusionGKT-137831 improves erectile function by 70% in type 1 DMED rats and constitutes a promising compound for the treatment of type 1 DMED, likely by inhibition of overactivated oxidative stress, down-regulation of proinflammatory factors, and amelioration of excessive autophagy and endothelial function.B Zhou, Y Chen, H Yuan, et al. NOX1/4 Inhibitor GKT-137831 Improves Erectile Function in Diabetic Rats by ROS Reduction and Endothelial Nitric Oxide Synthase Reconstitution. J Sex Med 2021;18:1970–1983.

Epigraphy and Ambition: Building Inscriptions in the Hinterland of Carthage

abstractBuilding inscriptions are not a good proxy for building activity or, by extension, prosperity. In the part of Roman North Africa where they are the most common, the majority of surviving building inscriptions document the construction of religious buildings by holders of local priesthoods, usually of the imperial cult. The rise of such texts in the second centurya.d., and their demise in the early third century, have no parallel in the epigraphic evidence for other types of construction, and should not be used as evidence for the pace of construction overall. Rather than economic change, these developments reflect shifts in the prospects of aspirational local elites, for whom priesthoods served as springboards to more prestigious positions. These positions were linked to Carthage through administrative arrangements that made this city the metropolis for scores of dependent towns and their ambitious elites.

Polityka językowa w Polsce a wpływ języka angielskiego na polszczyznę

Language Policy in Poland in the Context of the Impact of English on Polish&#x0D; The paper examines the way and the extent to which language policies have affected the development of the Polish language. However, the purpose of the present paper is to highlight the change in attitude towards the increasing impact of English on Polish. The influence of English became more prominent in Poland after the change in the political system in 1989, and has for the most part been in the area of lexical borrowings. However, the influence of English is not only restricted to the inflow of English loanwords, but also extends to their relatively high frequency of usage. In addition, there is evidence of other types of influence that are non-lexical. However, the impact of English on Polish has not been as extensive as is claimed by some Polish linguists who since the early 1990s have lamented over the decline of the Polish language caused by the ”flood” of British and American English borrowings. Indeed, the status of English as a lingua franca was considered itself to be a threat to Polish, with even the possibility of the extinction of the tongue. This concern about language purity led to the creation of the Polish Language Council in 1996, whose aim has been to advise on and describe (rather than prescribe) linguistic behaviours among Polish language users. This legislative body was behind the Polish Language Act passed in 1999. Its purpose, however, has been to protect Polish rather than to purify it and to minimize the foreign influences (which mainly refer to English) rather than to eradicate them. Since the beginning of the 21st century, the Polish linguists’ attitude towards the ”Anglicization” of the Polish language has changed dramatically and it is now believed that the influence of English makes Polish richer and more globalized.

Voter Beliefs and Strategic Voting in Two-Round Elections

How widespread is strategic voting in two-round electoral systems, and which types of voters are most likely to engage in such behavior? While runoff elections are common in presidential systems around the world, research on strategic voting in these settings remains limited. This paper explores four different types of strategic behavior that are possible in two-round systems, including some types, such as “strong-to-weak” strategic voting, which are not possible in single-shot elections. We use a nationwide survey to assess the incidence and correlates of strategic voting in Brazil’s 2018 presidential election, where thirteen candidates competed in the first round. We find evidence of “weak-to-strong” strategic voting at a similar rate to that documented in single-round elections in other countries. We find little evidence of other types of strategic voting. Furthermore, we show that voters’ confidence in their predictions of the likely electoral outcome and their ideological preferences strongly predict strategic voting. These results point to the importance of accounting for voter beliefs and attitudes in addition to objective voter characteristics to explain strategic voting.

Associated liver partition and portal vein ligation for staged hepatectomy: a review.

Outcomes of liver resection have improved with advances in surgical techniques, improvements in critical care and expansion of resectability criteria. However, morbidity and mortality following liver resection continue to plague surgeons. Post-hepatectomy liver failure (PHLF) due to inadequate future liver remnant (FLR) is an important cause of morbidity and mortality following liver resection. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel two-staged procedure described in 2012, which aims to induce rapid hypertrophy of the FLR unlike conventional two-stage hepatectomy, which require a longer time for FLR hypertrophy. Careful patient selection and modifications in surgical technique has improved morbidity and mortality rates in ALPPS. Colorectal liver metastases (CRLM) confers the best outcomes post-ALPPS. Patients <60 years old and low-grade fibrosis with underlying hepatocellular carcinoma (HCC) are also eligible for ALPPS. Evidence for other types of cancers is less promising. Current studies, though limited, demonstrate that ALPPS has comparable oncological outcomes with conventional two-stage hepatectomy. Modifications such as partial-ALPPS and mini-ALPPS have shown improved morbidity and mortality compared to classic ALPPS. ALPPS may be superior to conventional two-stage hepatectomy in carefully selected groups of patients and has a promising outlook in liver surgery.

CANNABIS USE IN THE AGE OF LEGALIZATION: IMPLICATIONS FOR THE GERIATRIC POPULATION

The prevalence of cannabis use among older adults has significantly increased in recent years. This trend likely captures the attitudes of the aging Baby Boomer generation as well as the spread of laws legalizing cannabis across the United States. As cannabis usage becomes more common in older adults, physicians must remain up to date regarding how cannabis is accessed and consumed, the types of strains and products sold in dispensaries, the indications and efficacy of FDA approved forms, as well as the different effects of tetrahydrocannabinol (THC) and cannabidiol (CBD). Despite the significant increase in cannabis use, there remains a paucity of evidence on the efficacy and safety in older adults. From a harm reduction standpoint, data regarding the safety profile of cannabis is essential since aging is typically associated with changes in pharmacokinetics and pharmacodynamics, multimorbidity, increase in prescription medication utilization and declines in function. Of particular importance in the geriatric population are the associations between cannabis and cognition, falls and injury, drug interactions, pain modulation and treatment of dementia related agitation. In terms of cognition and memory, heavy cannabis use has been traditionally associated with negative neurocognitive consequences. Interestingly, new animal models have found that low dose THC may actually improve memory and cognition in old animals, although how this data will translate to humans remains unclear. Next, commonly experienced side effects of cannabis in the elderly include dizziness, hypotension, drowsiness and confusion, all of which may impact fall risk. The risk of side effects may be compounded when considering interactions with other prescribed medications. In terms of pain modulation, although physicians may seek non-opioid pain regimens for geriatric patients, there is low-strength evidence that cannabis alleviates neuropathic pain and insufficient evidence for other types of pain. Finally, data does not yet support the usage of cannabis to improve neuropsychiatric symptoms in dementia patients. While physician knowledge of legalities, usage trends, indications and adverse effects of cannabis is necessary to manage medically and socially complex aging patients, this remains challenging in the setting of a very limited evidence-base.

Theoretical Aspects of Providing Evidence in Administrative Process

The article deals with theoretical aspects of providing evidence in administrative process. Attention is drawn to the importance of evidence for administrative procedural practice. It is concluded that the administrative process is aimed at understanding the truth in the context of administrative cases. At the same time, evidence in administrative proceedings has its own features that distinguish it from evidence in other types of legal proceedings. One of the major shortcomings is the lack of systematization of administrative and procedural rules. It is noted that the measures of administrative and procedural support are twofold in nature. On the one hand, they can be aim at collecting evidence, on the other hand — at administrative-procedural prevention of offenses and drafting of administrative-procedural documents. An attempt has been made to substantiate that the process of providing evidence is present not only in such traditional administrative proceedings as proceedings in cases of administrative offenses or in administrative and disciplinary proceedings, but also in administrative and procedural proceedings. Attention has been focused on types of administrative and procedural actions undertaken in the process of providing evidence in administrative and procedural proceedings.

Plastome phylogenomics and characterization of rare genomic changes as taxonomic markers in plastome groups 1 and 2 Poeae (Pooideae; Poaceae).

A phylogenomic analysis of 42 complete plastid genomes (plastomes), including 16 that were newly sequenced, was conducted. Plastomes were sampled from 19 subtribes of Pooideae, to investigate relationships within and between Chloroplast Group 1 (Aveneae) and Group 2 (Poeae) species. Two data partitions: complete plastomes, and a combined plastome and rare genomic change (RGC) data matrix, were analyzed. Overall, 156 non-ambiguous RGC were identified, of which homology was inferred for 38 RGC. Among the 38 RGC identified, six were synapomorphic among the Group 1 subtribes: Aveninae, Agrostidinae, and Anthoxanthinae, (Phalaridinae + Torreyochloinae), and 27 were synapomorphic among the Group 2 subtribes: Loliinae, (Ammochloinae + Parapholiinae + Dactylidinae), Parapholiinae, Dactylidinae, Poinae, and Coleanthinae. Four RGC were determined to be homoplasious in Groups 1 and 2. Two other RGC originated through intrastrand deletion events. The remaining RGC events likely originated through recombination given their size and lack of sequence evidence for other types of mutations. This study also determined that relationships between taxa, even those only weakly supported in previous studies, could be inferred with strong support when utilizing complete plastomes.

Policies to Prevent Illegal Acquisition of Firearms: Impacts on Diversions of Guns for Criminal Use, Violence, and Suicide

Firearm-related deaths are a significant source of mortality in the USA. More than 30,000 individuals die annually from firearm-related injuries, including homicide and suicide, in our nation. This review summarizes recent findings on policies designed to prevent illegal acquisition of firearms and their impacts on diversions of guns into underground markets and firearm-related homicide and suicide. A significant body of evidence has been produced between 2013 and 2018 demonstrating the effectiveness of laws requiring prospective handgun purchasers to obtain a permit (PTP). The evidence for other types of laws to deter illegal acquisition of firearms is less robust. Current research on illegal acquisition and the impact of related policies illustrates that there are policies that effectively reduce diversion and have positive impacts on firearm-related violence. However, there is a paucity of research that use strong study designs and clearly identifies specific policy impacts pertaining to diversion and illegal acquisition of firearms. Future research is needed that further elucidates transactions that facilitate a gun’s entry into an underground market and the role and impact of policies regulating these transactions.

Memantine for dementia.

Memantine for dementia.