Karl Grassmann's 1896 paper "critical overview of contemporary theories of the heredity of the psychoses".

Four years before the rediscovery of Mendel's work in 1900, Karl Grassmann published a detailed, scholarly review of the heredity of psychosis which we here review. A full translation is in the appendix. We emphasize seven major conclusions from this review.

A simulation-enhanced, spaced learning, interprofessional "code blue" curriculum improves ACLS algorithm adherence and trainee resuscitation skill confidence.

In-hospital cardiac arrest resuscitation training often happens in silos, with minimal interprofessional training. The aim of this study was to implement and evaluate a simulation-enhanced, interprofessional cardiac arrest curriculum in a university hospital. The curriculum ran monthly for 12 months, training interprofessional teams of internal medicine residents, nurses, respiratory therapists, and pharmacy residents.

Impact of tobacco flavoring on oral nicotine consumption in C57BL/6J mice.

Background: The continued use of flavors in tobacco products has been a prominent factor in their popularity, yet little is known regarding their role in nicotine dependence. This study aimed to investigate the impact of tobacco flavoring on oral nicotine consumption in mice using the two-bottle choice (2BC) test and assessed the potential impact of age and sex in their interactions.

Methods: Adolescent and adult male and female C57BL/6J mice were used.

Fatigue Failure of Semiconstrained Total Knee Replacement: Magnetic Resonance Imaging Diagnosis With Tips and Tricks for Extraction and Reconstruction.

Modular components allow for the precise adjustment of sizing and balancing in knee replacement and are widely used in revision total knee arthroplasty. While they have a significant advantage over monoblock implants, these components may be associated with fretting and corrosion at modular junctions. We report the case of a fracture of a morse taper adapter bolt in a 65-year-old female with a history of multiple revision knee arthroplasties.

Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice.

Background: Because of their implications in several pathological conditions, α4β2* nicotinic acetylcholine receptors (nAChRs) are potential targets for the treatment of nicotine dependence, pain, and many psychiatric and neurodegenerative diseases. However, they exist in various subtypes, and finding selective tools to investigate them has proved challenging. The nicotinic receptor agonist, 5-iodo-A-85380 (5IA), has helped in delineating the function of β2-containing subtypes in vitro; however, much is still unknown about its behavioral effects.

Ablating Persistent Atrial Fibrillation - Still Learning While Burning!

Pulmonary vein isolation (PVI) remains the cornerstone of atrial fibrillation (AF) ablation for both paroxysmal and persistent AF; however, the rates of freedom from arrhythmia observed after PVI for persistent AF are markedly lower compared with the rates observed for paroxysmal AF. Inexorable atrial structural and electrical remodeling in AF leads to an arrhythmogenic substrate that favors the genesis and perpetuation of persistent AF. The pathogenesis of paroxysmal AF differs from that of persistent AF.

Clinical Outcomes are Similar Between Graft Types Used in Chronic Patellar Tendon Reconstruction: A Systematic Review.

Purpose: To compare clinical outcomes between graft types and techniques used to repair chronic patellar tendon injuries to help surgeons make evidence-based decisions.

Methods: Medline, Embase, and Cochrane libraries were searched through January 2021, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Inclusion criteria were surgical treatment of chronic patellar tendon injury (defined as >6 weeks old), article available in English, and human subjects, minimum 1-year follow-up, and level of evidence I-IV.

Hermann Hoffmann's 1921 Monograph: "The Offspring of Endogenous Psychoses: Genealogical-Characterological Examinations".

Five years after the publication of Rüdin's major sibling study, Hermann Hoffmann, working with Rüdin, performed the first systematic study of the risk for dementia praecox (DP) in offspring of DP probands. Field work was limited to 3 months. Hoffmann ascertained families with at least one parent with certain DP, after Kraepelin, with children the youngest of whom were at least 30 years old.

Bruno Schulz's 1933 Monograph: On the Hereditary Etiology of Schizophrenia.

In his 1933 article, Bruno Schulz reported a follow-up and reanalysis of the schizophrenic probands and their relatives first studied by Rüdin 20 years earlier that sought to clarify whether schizophrenia was a valid "unit-character" for Mendelian genetic analysis. He proposed a range of subgroupings of probands, particularly traditional subtyping, presence or absence of identifiable causal influences, and outcome. He then compared those subgroupings in several ways, most commonly by the risk for schizophrenia in their siblings and by the level of resemblance among proband-sibling affected pairs.

Rüdin's 1916 Monograph: On the Inheritance and Primary Origin of Dementia Praecox.

In 1916, Ernst Rüdin published the first modern family study in the history of psychiatric genetics, the major goal of which was to test whether the pattern of risk in the siblings of dementia praecox (DP) probands followed Mendelian expectations. He utilized systematic ascertainment of probands and multisourced diagnostic assessments of probands and relatives, applying the narrow Kraepelinian concept of DP. In a novel step, he collaborated closely with a statistical geneticist-Wilhelm Weinberg-and applied his sibling, proband, and age correction methods.

The Beginnings of Scientific Psychiatric Twin Research: Luxenburger's 1928 "Preliminary Report on the Psychiatric Examination of a Series of Twins".

While reports of twin pairs concordant for insanity began to appear in the 19th century, the first modern psychiatric twin study that fulfilled Galton's 1875 promise of the value of the twin method was published by the German Psychiatrist and Geneticist Hans Luxenburger in 1928. Luxenburger introduced four major methodological advances: the use of representative sampling, proband-wise concordance, rigorous zygosity diagnoses, and age correction. He used a narrow Kraepelinian diagnostic approach diagnosis and ascertained twins hospitalized, on a specific day, in all large Bavarian asylums.

Bruno Schulz and his 1926 Article: "Regarding the Problem of Determining Hereditary Prognosis. The Affliction Prospects for Nephews and Nieces of Schizophrenics".

Authored by one of Rüdin's most productive colleagues, Bruno Schulz, the main goal of this article was to estimate risk for dementia praecox (DP) in nieces/nephews (n/n) of DP probands to address practical questions for genetic counseling. Schulz selected 76 primary probands from records of the genealogical department of the German Research Institute of Psychiatry who both had DP and had siblings-secondary probands-with children aged 20 years or greater. Those children had a morbid risk for DP of 1.

Integrin binding peptides facilitate growth and interconnected vascular-like network formation of rat primary cortical vascular endothelial cells .

Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells.

Pharmacologic Therapies to Promote Recovery of Consciousness.

Pharmacologic interventions are commonly used to support rehabilitation efforts of patients with disorders of consciousness (DoC). The 2018 practice guidelines recommend amantadine in adults with traumatic DoC to promote functional recovery, though several other stimulants are used off-label in clinical practice and trials, such as methylphenidate, bromocriptine, levodopa, and zolpidem. Differences in the mechanisms of action, adverse effects, pharmacokinetics, and drug-drug interactions should be considered when selecting the best agent for each individual patient.

Persistent sensory changes and sex differences in transgenic mice conditionally expressing HIV-1 Tat regulatory protein.

HIV-associated sensory neuropathies (HIV-SN) are prevalent in >50% of patients aged over 45 years many of which report moderate to severe chronic pain. Previous preclinical studies have investigated the mechanisms by which HIV-1 causes sensory neuropathies and pain-like behaviors. The aim of the present study is to delineate the role of chronic HIV-1 trans-activator of transcription protein (Tat) exposure in the development of neuropathy in mice.

Edward Spitzka's 1883 Textbook: The Psychiatric Nosology That Kraepelin Inherited and Transformed.

Edward Spitzka, a prominent New York-based alienist, who spent 3 years in Germany studying psychiatry, published a textbook in 1883-the same year as the first edition of Kraepelin's textbook-that contained detailed descriptions of all the seven psychiatric syndromes that formed the basis of Kraepelin's nosologic synthesis: mania, melancholia, katatonia, secondary deteriorations, hebephrenia, circular insanity, and monomania. A study of this text provides us with a "before" picture-a view of the canvas of psychiatric diagnostic categories-from which Kraepelin worked. Studying what Spitzka's diagnostic categories contain and what they are missing highlights the key steps Kraepelin took in the development of his nosologic synthesis.

Ludvig Dahl's psychiatric genetic studies in his 1859 monograph: "Contribution to the knowledge of insanity in Norway".

In 1859, Ludvig Dahl, a Norwegian alienist, wrote a rarely referenced book entitled "Contribution to The Knowledge of Insanity." In it, he describes a highly innovative psychiatric genetics research project with severable notable features. First, while the vast majority of 19th century psychiatric genetic studies were based on asylum hospital records, Dahl did field work to find cases of mental illness in certain defined areas within Norway, using census data, key-informants, record reviews, and personal interviews especially of suspected affected individuals.

From 2-Triethylammonium Ethyl Ether of 4-Stilbenol (MG624) to Selective Small-Molecule Antagonists of Human α9α10 Nicotinic Receptor by Modifications at the Ammonium Ethyl Residue.

Nicotinic acetylcholine receptors containing α9 subunits (α9*-nAChRs) are potential druggable targets arousing great interest for pain treatment alternative to opioids. Nonpeptidic small molecules selectively acting as α9*-nAChRs antagonists still remain an unattained goal. Here, through modifications of the cationic head and the ethylene linker, we have converted the 2-triethylammonium ethyl ether of 4-stilbenol (MG624), a well-known α7- and α9*-nAChRs antagonist, into some selective antagonists of human α9*-nAChR.

Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities.

Understanding which biological pathways are specific versus general across diagnostic categories and levels of symptom severity is critical to improving nosology and treatment of psychopathology. Here, we combine transdiagnostic and dimensional approaches to genetic discovery for the first time, conducting a novel multivariate genome-wide association study of eight psychiatric symptoms and disorders broadly related to mood disturbance and psychosis. We identify two transdiagnostic genetic liabilities that distinguish between common forms of psychopathology versus rarer forms of serious mental illness.

Medical genetics in the 19th century as background to the development of psychiatric genetics.

This article examines the relationship between the early efforts of alienists to understand the role of heredity in the etiology of insanity in the 19th century and the parallel efforts of the nascent discipline of medical genetics. I review three monographs on general medical genetics: Adams in 1814, Steinau in 1843, and Lithgow in 1889. Numerous parallels were seen between their writings and those of their contemporary alienists working on mental disorders including (i) an emphasis on the transmission of the liability to illness rather than the illness itself, (ii) discussions of the homogeneous versus heterogeneous nature of familial transmission of disease, (iii) the relative value of direct versus indirect hereditary effects, (iv) the role of mothers versus fathers in transmitting liability, (v) possible environmental sources of familial clustering, and (vi) the transmission of age at onset of illness.

Genotypic Differences in the Effects of Menthol on Nicotine Intake and Preference in Mice.

Menthol has been shown to exacerbate elements of nicotine addiction in humans and rodents; however, the mechanisms mediating its effects are not fully understood. This study examined the impact of genetic factors in menthol's effects on oral nicotine consumption by comparing two inbred mouse strains with differing sensitivities to nicotine. C57BL/6J (B6J) mice are nicotine-preferring, while DBA/2J (D2J) mice are not.

Formulated Curcumin Prevents Paclitaxel-Induced Peripheral Neuropathy through Reduction in Neuroinflammation by Modulation of α7 Nicotinic Acetylcholine Receptors.

Paclitaxel is widely used in the treatment of various types of solid malignancies. Paclitaxel-induced peripheral neuropathy (PIPN) is often characterized by burning pain, cold, and mechanical allodynia in patients. Currently, specific pharmacological treatments against PIPN are lacking.

Inactivation of fatty acid amide hydrolase protects against ischemic reperfusion injury-induced renal fibrogenesis.

Although cannabinoid receptors (CB) are recognized as targets for renal fibrosis, the roles of endogenous cannabinoid anandamide (AEA) and its primary hydrolytic enzyme, fatty acid amide hydrolase (FAAH), in renal fibrogenesis remain unclear. The present study used a mouse model of post-ischemia-reperfusion renal injury (PIR) to test the hypothesis that FAAH participates in the renal fibrogenesis. Our results demonstrated that PIR showed upregulated expression of FAAH in renal proximal tubules, accompanied with decreased AEA levels in kidneys.