Clinical effectiveness of unilateral deep brain stimulation in Tourette syndrome

Dysfunctional basal ganglia loops are thought to underlie the clinical picture of Tourette syndrome (TS). By altering dopaminergic activity in the affected neural structures, bilateral deep brain stimulation is assumed to have a modulatory effect on dopamine transmission resulting in an amelioration of tics. While the majority of published case reports deals with the application of bilateral stimulation, the present study aims at informing about the high effectiveness of unilateral stimulation of pallidal and nigral thalamic territories in TS. Potential implications and gains of the unilateral approach are discussed

ОТТОРЖЕНИЕ СЕРДЕЧНОГО ТРАНСПЛАНТАТА И НЕИНВАЗИВНЫЕ ПОКАЗАТЕЛИ ФУНКЦИОНАЛЬНОГО СОСТОЯНИЯ СТЕНКИ ОБЩЕЙ СОННОЙ АРТЕРИИ

Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW) variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts). Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD) pts without decompensated heart failure were included. Along with resistive index (Ri), pulsative index (Pi), and CCW intima-media thickness (IMT), CCW rigidity index (iRIG) was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7%) and 17 (18.3%) cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001). Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9) sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84.3%. Conclusions. Increased carotid wall stiffness is found in patients with both antibody-mediated and cellular car- diac allograft rejection. Non-invasive measurement of carotid artery wall rigidity index with triplex ultrasound is a simple screening tool for risk stratification. Having a functional marker would enable preventive measures to be taken at the early stages. Введение. Отторжение сердечного трансплантата может сопровождаться повышением содержания в крови определенных биомаркеров, которые могут оказывать влияние на эластические свойства сте- нок артерий. Согласно нашей гипотезе, показатели функционального состояния общей сонной арте- рии (ОСА) могут быть использованы в качестве неинвазивных маркеров при скрининге отторжения трансплантированного сердца (ТС). Цель исследования. Изучить возможность применения методов ультрасонографической оценки функционального состояния стенки ОСА для неинвазивного скри- нинга отторжения сердечного трансплантата. Методы. В исследование включен 171 больной, из них 93 реципиента ТС, 30 больных дилятационной кардиомиопатией (ДКМП) с терминальной сердечной недостаточностью (СН) и 48 больных ИБС без декомпенсации СН. При помощи ультрасонографичес- кого исследования у обследуемых больных определялись резистивный индекс (Ri), пульсативный ин- декс (Pi), толщина комплекса интима–медиа (ТИМ) ОСА и индекс ригидности ОСА(iRIG), рассчиты- ваемый по эмпирической формуле. Неинвазивные исследования у пациентов после ТС проводились до выполнения эндомиокардиальной биопсии (ЭМБ). Результаты. Средние значения Ri, Pi и ТИМ ОСА в исследуемых подгруппах не отличались. Значения показателя iRIG у больных ИБС были достоверно ниже, чем у больных ДКМП и реципиентов без признаков отторжения (в последних двух подгруппах достоверных различий не выявлено). Признаки гуморального (ГО) и клеточного отторжения (КО) по результатам ЭМБ были выявлены у 22 (23,7%) и 17 (18,3%) реципиентов соответственно. Средние значения показателя iRIG у реципиентов без отторжения трансплантата были достоверно ниже по сравнению с пациентами с признаками ГО и КО (5514,7 ± 2404,0 против 11856,1 ± 6643,5 и 16071,9 ± 10029,1 см/сек2 соответственно, p = 0,001). Площадь под кривой ROC для показателя iRIG была 0,90 ± 0,03 ед2. Анализ показал, что у лиц со значениями показателя iRIG, превышающими расчетное поро- говое значение 7172 см/сек2, относительный риск выявления отторжения при проведении ЭМБ состав- ляет 17,7 (95% ДИ = 6,3–49,9); чувствительность показателя в качестве неинвазивного маркера оттор- жения составляет 80,5%, специфичность – 81,1%, негативная предсказательная значимость – 84,3%. Выводы. У реципиентов сердечного трансплантата с признаками отторжения повышается ригидность стенки ОСА. Определение значения показателя ригидности ОСА при помощи неинвазивного ультра- сонографического исследования может быть использовано в качестве доступного метода скрининга отторжения ТС.

Population genomics of the Wolbachia endosymbiont in Drosophila melanogaster

Wolbachia are maternally-inherited symbiotic bacteria commonly found in arthropods, which are able to manipulate the reproduction of their host in order to maximise their transmission. Here we use whole genome resequencing data from 290 lines of Drosophila melanogaster from North America, Europe and Africa to predict Wolbachia infection status, estimate cytoplasmic genome copy number, and reconstruct Wolbachia and mtDNA genome sequences. Complete Wolbachia and mitochondrial genomes show congruent phylogenies, consistent with strict vertical transmission through the maternal cytoplasm and imperfect transmission of Wolbachia. Bayesian phylogenetic analysis reveals that the most recent common ancestor of all Wolbachia and mitochondrial genomes in D. melanogaster dates to around 8,000 years ago. We find evidence for a recent incomplete global replacement of ancestral Wolbachia and mtDNA lineages, which is likely to be one of several similar incomplete replacement events that have occurred since the out-of-Africa migration that allowed D. melanogaster to colonize worldwide habitats.Comment: 41 pages, 5 figure

Parallel Driving and Modulatory Pathways Link the Prefrontal Cortex and Thalamus

Pathways linking the thalamus and cortex mediate our daily shifts from states of attention to quiet rest, or sleep, yet little is known about their architecture in high-order neural systems associated with cognition, emotion and action. We provide novel evidence for neurochemical and synaptic specificity of two complementary circuits linking one such system, the prefrontal cortex with the ventral anterior thalamic nucleus in primates. One circuit originated from the neurochemical group of parvalbumin-positive thalamic neurons and projected focally through large terminals to the middle cortical layers, resembling ‘drivers’ in sensory pathways. Parvalbumin thalamic neurons, in turn, were innervated by small ‘modulatory’ type cortical terminals, forming asymmetric (presumed excitatory) synapses at thalamic sites enriched with the specialized metabotropic glutamate receptors. A second circuit had a complementary organization: it originated from the neurochemical group of calbindin-positive thalamic neurons and terminated through small ‘modulatory’ terminals over long distances in the superficial prefrontal layers. Calbindin thalamic neurons, in turn, were innervated by prefrontal axons through small and large terminals that formed asymmetric synapses preferentially at sites with ionotropic glutamate receptors, consistent with a driving pathway. The largely parallel thalamo-cortical pathways terminated among distinct and laminar-specific neurochemical classes of inhibitory neurons that differ markedly in inhibitory control. The balance of activation of these parallel circuits that link a high-order association cortex with the thalamus may allow shifts to different states of consciousness, in processes that are disrupted in psychiatric diseases

ТРАНСПЛАНТИРОВАННОЕ СЕРДЦЕ. ПРАВОЖЕЛУДОЧКОВАЯ НЕДОСТАТОЧНОСТЬ, ОТТОРЖЕНИЕ ИЛИ МИОКАРДИТ?

The differentiation of the cases of the right ventricular failure in transplanted heart should be complex and challenging. The 28-year old man with dilated cardiomyopathy underwent orthotopic heart transplantation. After transplantation developed right ventricular failure. The biopsy (n = 5) didn’t reveal any signs of myocardial rejection. There were noted some signs of inflammation in lateral right ventricular wall only by gated SPECT. The right ventricular failure increased and 6 months later there was successfully performed the heart retransplantation on the patient. The virusological study revealed the Epstein–Barr virus in myocardium. The explanted heart research excluded limphoproliferative disease by immunogystochemical tests. The final diagnosis is myocarditis. Дифференцирование причин правожелудочковой недостаточности пересаженного сердца должно быть комплексным. Мужчина 28 лет с дилатационной кардиомиопатией был подвергнут ортотопической трансплантации сердца. После трансплантации развилась прогрессирующая правожелудочковая недо- статочность. Биопсия (в количестве 5) не выявила признаков отторжения миокарда. Только при gated SPECT были отмечены признаки воспаления в боковой стенке ПЖ. Правожелудочковая недостаточность нарастала, и спустя 6 месяцев больному успешно была выполнена ретрансплантация сердца. Вирусоло- гическое исследование выявило наличие вируса Эпштейна–Барр в миокарде. Иммуногистохимические исследования эксплантированного сердца исключили лимфопролиферативное заболевание. Заключи- тельный диагноз – миокардит.

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. METHODS: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany ((n) = 135), Spain ((n) = 133), Switzerland ((n) = 20) and the United States ((n) = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). FINDINGS: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted (p)-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. INTERPRETATION: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2

Multiple cortical targets of one thalamic nucleus: the projections of the ventral medial nucleus in the cat studied with retrograde tracers

The organization of the cortical projections of the ventral medial thalamic nucleus (VM) was studied in the cat with retrograde tracers. The extent of the VM-cortical projections was first investigated with horseradish peroxidase injected in different cortical fields. The results obtained in the experiments indicated that the main target of VM efferents is represented by a large territory anterior to the cruciate sulcus involving area 6 and the gyrus proreus and extending into the anterior part of the medial cortical surface. The afferents to these precruciate fields arise from throughout the VM. In addition, the lateral third of VM projects upon the lateral precruciate cortex that is coextensive with the precruciate part of area 4, whereas VM efferents do not extend into the posterior sigmoid gyrus. A second major target of VM efferents is represented by the insular cortex in the anterior sylvian gyrus. VM projections also reach the prepyriform cortex and the cingulate gyrus. An anteroposterior decrease of density was found in the VM-cingulate projections. Sparse VM projections reach the temporal cortex, the adjacent posterior sylvian and ectosylvian fields, and the anterior ectosylvian gyrus. No VM projections were found either upon the visual areas 17 and 18 or upon the primary auditory cortex. The interrelations between some VM-cortical cell populations and their divergent collateralization were studied by using double retrograde labeling with fluorescent tracers. The results of these experiments demonstrated that a relatively high number (at least 20%) of VM cells projecting to the insula are also connected to the precruciate fields by means of axon collaterals. This finding indicates that VM is a highly collateralized structure of the cat's thalamus. Very few branched cells were found in the other combinations of cortical fields here examined (precruciate vs. posterior sylvian fields, lateral precruciate vs. proreal cortex, anterior vs. posterior cingulate fields). Altogether these data indicate that VM branched cells preferentially interconnect the two main cortical targets of the nucleus, i.e., precruciate and insular fields. The results of the present study are discussed in regard to the literature on the VM projections in the rat and the previously available data in the cat, to the afferent VM organization in the cat, to the relationships between VM and the nucleus submedius, and to the anatomical and functional role of VM in relation to the so-called "nonspecific" thalamocortical system