How the Inflamed Skull-Box Might Ruin the Cerebello-Cerebral Social Repertoire: Imaging, Testing, Rescuing with Currents.

Nascent cerebellar neuropsychiatry is rewriting complex human relations. In daily practice this sheds light on subsets of therapy-resistant patients, who feel hampered by a lack of skills in predictively presensing the trajectories to where especially their interpersonal appropriations might end up. Humans affected by "dysmetric" social phobia often lead minimal lives, strongly dislike exposition, suffer fatiguability also from immune dysfunctions, and anhedonia. In social dysmetria especially on the cerebellar cortex`s both lateralmost Crus-II (Van Overwalle) seem damaged, the left Crus-I may add agentic failure (Guell). The cerebellum, and the basal ganglia together discipline the cortex through parallel closed circuits partly interconnected through the thalamus. "Patho-trajectories" of the cere-bellum in daily care emerge through also neurological ataxiology and MRI-imaging. A uniquely pontine axonal diffusive damage to an executive-control-loop as core of "p-factor", the prime broad risk factor, points to an immune-arterial hotspot at the root of cerebellar arterial supply, as supported by the pediatric mostly inflammatory somatic "d-factor". While localizations refer back to his "phrenology", F. G. Gall's contention, that skulls, plausibly via mycobacteria, were relevant, are rehabilitated by calvario-menigeal vessels, which added the skull to the new brain logistics. Mast cells are uniquely positioned to cause superficial and deep cortical pathologies, and, en-closed in its subtentorial posterior fossa, also the cerebellum is exposed to various, often intracellular, smoldering originally dental or ORL-infections exemplifying non-neural psychiatric etiologies.

Immunopsychiatry of Infected Ears, Sinuses, Skulls, and Meninges: Mast Cells, Mozart, Van Gogh.

Medical psychiatry acquires more prominence in the biological field by new anatomical insights into the wrappings of the brain: meninges, but also Meningo-Calvarial Channels (MCCs) connecting the former with the bone marrows' also neuronally steered, functions. The skull-bone's meningeal arteries through migrating and orchestrating mast cells within a framework stressing their relations with arteries (Treviranus 2012-21) could explain enigmatic phenomena like migrainous and post-injury Cortical Spreading Depressions (CSD) or the Reversible Cerebral Vasoconstriction Syndrome (RCVS) escalating to "PRES". The skull might be accessed along chronic (para-)infectious paths resulting in Skull Bone Osteomyelitis (SBO) from the ear-nose-throat, dental and other microbiomes. Such paths seem promoted by compromised innate immune defenses: by "Mendelian" susceptibility, and/or acquired anti-INF-γ- or other auto-immunity or various microbial "Trojans" of e. g. meningeal myelo- and lymphocytes. These interact e. g. from the calvarial marrow niches onward. Hereby competing local and "intentional" intruding mast cells - by disturbing (or ingeniously boosting) cortical development and functioning - acquire relevance by interacting with arteries (Treviranus 2018, 2021). This predicts findings in behavior (Fitzpatrick & Morrow 2017) an "aortal" arterial biomechanical foundation of parasympathetic reverse arterio-intramural cerebro-interstitial drainage by CIMURAF/IPAD-2.0 (Treviranus 2018-21). Here the recent physiological re-conceptions of the skull illuminate own case histories through a gamut of possibly relevant neuro(-surgico)-psychiatric challenges. Among these meningo-cerebral immune, vasospastic, and cystic processes some generate broad "experiential" hallucinations, which may slowly transit to true psychoses through "perfect crime lesions" of neurons and glia by tryptase-armed mast cells descending into parenchyma often congested by "push-back". These emerging hypotheses coalesce in advancing an integrative macro-medical psychiatry and even the pathography of Van Gogh and Mozart stressing the benign and creative roles of mast cells.

Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma.

Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study was comprised of a G100 dose escalation (5 or 10 µg/dose, or 20 µg/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 µg/dose expansion. Adverse events grade ≥3 were uncommon in patients treated with G100, and no unexpected toxicities were observed when combined with pembrolizumab. G100 20 µg (n = 18) resulted in an overall response rate of 33.3% and abscopal tumor regression in 72.2% of patients. This early-phase study provides a foundation for combining an intratumoral TLR4 agonist with agents to produce immune-mediated responses in follicular lymphoma with limited added toxicity.

The Pandemic`s Unresolved Infectious Psycho-Neuro-Immunologies: Myeloid Cells, Vessels, Nasal Cross-Roads.

Unresolved infectious psycho-neuro-endocrino-inflammation (PNEI) denotes an area of tragically accelerated interest because of SARS-CoV-2`s capacity to meddle with the immune responses in a stage-wise fashion. Its pandemic, interacting with antecedent further deteriorating health and living conditions, takes a direct toll of million human lives. In order to withstand the plethora of slowly or never easing ailments labeled "Post-acute Sequelae of Covid-19 (PASC)" a comprehensive understanding from the intrusions up to its emerging aftermaths is paramount. For the strained health professions these prospect care requirements of 1 in 5 for a non-convalescence overlapping also with other tedious long-hauling "triggered" disorders adjacent to psychiatry like chronic fatigue with orthostasis intolerance or intracranial hypertension (ME/CFS-OI; IIH). For the lattter two new pathophysiologies are proposed in order to inform a strong rehabilitative psychiatric liaison not referring sufferers to a psychiatric "enigmo-somatic bin", but to an invigorated somato-psychic care e. g. for exertional malaise. Starting from early stimulation of escalating myeloid-derived suppressor cells the neglected mast cells show up (for now without their lymphatic partners) as ambivalent core participants. They interact or orchestrate or sequentially explode in etosis guarding or breaking sane barriers especially at cerebral arteries. In Covid-19 they seem unleashed at the blood-brain-barrier by the early virally invaded nasal ganglia, which plausibly mis-direct the quickest interstitial arterio-intramural outflow - thus a.) losing its ability to "comply" with pulsatile flow through varying the width of its sliding chambers causing ME/CFS-Orthostatic Intolerance and b.) inflaming and stiffening the brain's interstitium through a "push-back" outpacing the confuted inventive "glymphatic-1.0" model. Mast cells - colonized or not - plausibly permeabilize the choroid plexus and venous or bony brain barriers co-causing the not so rare Idiopathic Intracranial Hypertension. Innate memory - as activated by short RNAs through BCG-vaccinations directed against the permanent TBC-pandemic leads to hopes for a hastening of resolutions through a combined medical, exertional, psychosocial, and psychiatric rehabilitation informed by a new "PNEI" - paving the way for amplified-BCG or future psychiatric vaccinations.

Substance-Related Found-Down Compartment Syndrome: A Systematic Review.

OBJECTIVE: To characterize the patient population with substance-related found-down extremity compartment syndrome (FDECS) and report on their treatment and outcome. DATA SOURCE: This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Articles in English language were identified by searching 3 online databases, EMBASE, PubMed Publisher, and Cochrane Central, in September 2019. STUDY SELECTION: Studies involving substance-related FDECS were included. Exclusion criteria were as follows: patient age <18 years, not original studies, no full text available, technical reports, traumatic acute extremity compartment syndrome, chronic exertional compartment syndrome, and vascular acute extremity compartment syndrome. DATA EXTRACTION: There were 61 studies included with 166 cases of FDECS. Two investigators screened and extracted data independently according to a standardized template. Disagreements were addressed by an attempt to reach a consensus, and involvement of a third reviewer. Studies were quality assessed with "Quality Assessment tool for Case Series Studies." DATA SYNTHESIS: Descriptive statistics were reported using Excel. CONCLUSION: Substance-related FDECS is often occurring in young adults. Data from this review found that most of the patients were already diagnosed with substance use disorders and/or psychiatric disorders. There should be a high index of suspicion of FDECS in patients presenting after prolonged immobilization. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Psychoses by Attacks from Subverted Mast Cells: A Role for Arterial Intramural Flow Badly Steered by the Nasal Ganglia?

Mechanisms of cortical psychoses are approached by complementing big data-driven genetics and imaging with a putatively subverted neurovascular "reverse plumbing" by arteries. The "cortical spread" of grey matter loss in schizophrenia and the mid-pericallosal "congestion" in fMRI of periodic catatonia - treatable electromagnetically along arteries - are interpreted in terms of the fastest interstitial outflow through the Cerebral IntraMural Reverse Arterial Flow-engine (CIMURAF, Treviranus 2018-19) draining "waste" via arterio-adventitial lymphatics to the neck. Such repetitively sliding segments of CIMURAF are wrung downstream by muscles likely steered by the neurovascular pterygopalatine ganglion. At the pericallosal artery, along its ideal long straight segment, this likely happens diverging from the mid-callosum towards the front and the back. In the case of a convergent inversion a mid-callosal clash will result, which is observable in psychoses as a mid-callosal high-flow-spot simultaneously with hyper-perfusions of branches and "backwatering" of pial vessels with reactive waste - till date interpreted psycho-mathematically. CIMURAF might also accelerate the perivascular intrusion of MCs by flushing autocrine signals (of which electro-magnetism moves the dipoles) through a putative periadventitial counter-current. Psychoses plausible occur through tryptase-mediated attacks operated by mast cells against oligodendrocytes' cytoskeleton (Medic 2009) and probably via complement-4 (Schizophrenia WG, 2014) against neurons. Usually MCs are essential long-lived "orchestrators" of homeostases and immune or barrier defences interacting with nerves, immunocytes, organs, and routes. MCs after somatic programming as to "destination & destiny" (Treviranus 2017a, 6.2., 2018) rapidly intrude also into the brain's parenchyma, first within the lymphatics and then putatively by crossing-over to extraluminal arterial routes. MCs transverse the BBBs, while macrophages only trespass in "disease" (Faraco et al. 2017). Both can be "subverted" by a list of microbes (and putatively blown up by COVID-19 within walls). Enuresis and MCs' reactions to clozapine add to the interactive support from (epi-)genetics and imaging.

Mast cell autocrinicity near cerebral arterial wall "reverse glymphatic flow" as prime target of electromagnetic effects.

Efforts to disclose the mechanisms of transcranial therapeutic electro-magnetic fields (EMF) acting on the brain's cells (Marino, Kibleur) and recently immune cells (Gülöksüz) meet unsolved physiological details of blood vessels, exclusively arterial vasomotion or the non-glial-related former g(lia)-lymphatic flow (Iliff; Liu DX) - now replaced by an astrocytic AQP4-pipeline cooling the brain (Nakada 2014). Here within the convergent dyn4TAM-framework, which had suggested the first mast cell behavioral experiment (Fitzpatrick & Morrow 2017), three intertwined physiological concepts are contributed: A) "autocrinicity" - how flushed, thus absent, autocrine signals integrate external fluidics into cellular computations e.g. on motility: EMFs could increase such absences by targeting e.g. dipole-cytokines; B) a new concept of the arterial wall based on a tangible interpretation of the coronal histology of all arteries as a co-axial pulse-dampening engine (Treviranus 2012). In the brain this engine might provide the quickest cerebral outflow via the Cerebral IntraMUral Reverse Arterial Flow (Treviranus 2018b), while transmitting further forces acting upstream to the paravascular spaces; C) some key roles for mast cells in neuro-psychiatry (Silver & Curley 2013) and their interactive lymphatic and non-luminal vascular routes to the brain dictated by peripheral imprinting as to destiny (Csaba 1987) and destination (Treviranus 2013). Within the skull they might advance against para-arterial upstream currents. Some known causal mediators of the effects of transcranially applied EFMs and puzzling results are then put tentatively in perspective with the above "tangible" models, e.g. by aligning probable induced currents with arterial segments or the new direct meningeal-calvario-myeloid channels. RESULTS: The case for a role of mast cells and diverse flows in transcranial electromagnetic brain therapy seems promising.

Rescue of the Appropriative "Thought-Action-Mood" Space: Anatomy and Mast Cells Generate "Mixable" Dimensions in Language and Statistics.

BACKGROUND: The orthogonal axes of Thought (T), Action (A), and Mood (M) span a phase space which corresponds e.g. to the three medial thalamic areas related to three resonating cortico-subcortico-thalamo-cortical loops. The above three of several loops constitute an "appropriative engine", since within that space, as hinted to via Fig. 228 by Emil Kraepelin to illustrate bipolar mixed states, circular waves of appropriative functioning - from need via action to e.g. satisfaction - reflect a spectrum of temperamental to anxio-affective signatures of sequential appropriation waves. This neo-classical "dyn4TAM"-model also posits that a prime (thalamic) motivating system of Uncertainty-orientation (R. M. Sorrentino) regulates the temperamental balance between only 4-dimensional (D)-"Thought" (G. Halford) about effort-sparing models and high-D-"Action" (G. Rizzolatti) meaningfully related to movement. In fact the exchange across this "complexity divide" - between "grasping" action-related high-D-modules and "calculating" 4D-modules of brains - even concerns the grounding of symbolic relational "concepts. " It thus expands on the Franco-Kraepelinian "TAM"-System (FKS) which suffered a distortion by Kraepelin and the eliminative eugenicist Wilhelm Weygandt, unfortunately carried on in the "bipolar spectrum" current. Because the above loops are independently segregated they generate true dimensions. Furthermore the phenomena they jointly create become patterns, i.e. independently filled slots. Now these are irremediably destroyed at acquisition by Galtonian statistics which is detrimental to conceiving dimensional topics. HYPOTHESIS: Here we posit that preponderantly "uncertainty-oriented", calculating academics unless depressed, are attracted by 4D-Thought and repulsed by intuition. They thus avoid bio-psychologically the " comprehension" of patterns. METHOD & RESULT: New research initiated by dyn4TAM confirmed, that the homologous rodent sign-tracking depends on mast cells modulating the ACC-loop for "Action." CONCLUSION: The "complexity divide" warrants more attention in clinical and pure cognitive sciences and should include a "psychology of statistics".

Spray vaccination of chickens with an experimental vaccine against Newcastle disease.

Chickens, of various age groups, were vaccinated against Newcastle disease by spray vaccination with an experimental vaccine, designated V5K7E1. Aerosol spraying of 3-days-old chicks having a high titre of maternal antibodies failed to induce any obvious stimulation of haemagglutination-inhibiting antibodies. The chicks, when challenged 2 and 3 weeks after vaccination, were fully protected, but protection was inadequate when they were challenged 4 to 7 weeks after vaccination. Spray vaccination of 1-day-old specific-pathogen-free chicks resulted in the presence of antibodies at 7, 14 and 21 days. Subsequently the levels of antibodies declined progressively. The chicks resisted challenge up to 42 days after vaccination. Maternally immune chicks spray - vaccinated for the first time at 14 days showed a significant increase in antibodies and remained healthy when challenged at 10 weeks of age. Booster spray vaccination at 21 days of age subsequent to primary spray vaccination at 3 days of age, induced an anamnestic rise in antibody titre that persisted at protective levels for at least 66 days. Similarly, spray vaccination at 28 days, following administration of vaccine in the drinking water at 14 days, gave rise to high antibody titres which persisted for at least 70 days. In field trials, spray vaccination at the age of 3 days or 14 days provoked little or no apparent respiratory disturbance and was followed by an average mortality of 0.9% and 1.4% respectively.

Metabolic factors affecting enhanced phosphorus uptake by activated sludge.

Activated sludges obtained from the Rilling Road plant located at San Antonio, Tex., and from the Hyperion treatment plant located at Los Angeles, Calif., have the ability to remove all of the orthophosphate normally present in Tucson sewage within 3 hr after being added to the waste water. Phosphorus removal was independent of externally supplied sources of energy and ions, since orthophosphate and (32)P radioactivity were readily removed from tap water, glass-distilled water, and deionized water. Phosphorus uptake by Rilling sludge in the laboratory appears to be wholly biological, as it has an optimum pH range (7.7 to 9.7) and an optimum temperature range (24 to 37 C). It was inhibited by HgCl(2), iodoacetic acid, p-chloromercuribenzoic acid, NaN(3), and 2, 4-dinitrophenol (compounds that affect bacterial membrane permeability, sulfhydryl enzymes, and adenosine triphosphate synthesis). Uptake was inhibited by 1% NaCl but was not affected by 10(-3)m ethylenediaminetetraacetic acid disodium salt (a chelating agent for many metallic ions).