Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection.

BACKGROUND: A neurocognitive phenotype of post-COVID-19 infection has recently been described that is characterized by a lack of awareness of memory impairment (i.e., anosognosia), altered functional connectivity in the brain's default mode and limbic networks, and an elevated monocyte count. However, the relationship between these cognitive and brain functional connectivity alterations in the chronic phase with the level of cytokines during the acute phase has yet to be identified. AIM: Determine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6-9 months after infection. METHODS: We analyzed the predictive value of the concentration of acute cytokines (IL-1RA, IL-1ß, IL-6, IL-8, IFNγ, G-CSF, GM-CSF) (cytokine panel by multiplex immunoassay) in the plasma of 39 patients (mean age 59 yrs, 38-78) in relation to their anosognosia scores for memory deficits via stepwise linear regression. Then, associations between the different cytokines and brain functional connectivity patterns were analyzed by MRI and multivariate partial least squares correlations for the whole group. RESULTS: Stepwise regression modeling allowed us to show that acute TNFα levels predicted (R2 = 0.145; ß = -0.38; p = .017) and were associated (r = -0.587; p < .001) with scores of anosognosia for memory deficits observed 6-9 months post-infection. Finally, high TNFα levels were associated with hippocampal, temporal pole, accumbens nucleus, amygdala, and cerebellum connectivity. CONCLUSION: Increased plasma TNFα levels in the acute phase of COVID-19 predict the presence of long-term anosognosia scores and changes in limbic system functional connectivity.

Network connectivity determines cortical thinning in early Parkinson's disease progression.

Here we test the hypothesis that the neurodegenerative process in Parkinson's disease (PD) moves stereotypically along neural networks, possibly reflecting the spread of toxic alpha-synuclein molecules. PD patients (n = 105) and matched controls (n = 57) underwent T1-MRI at entry and 1 year later as part of the Parkinson's Progression Markers Initiative. Over this period, PD patients demonstrate significantly greater cortical thinning than controls in parts of the left occipital and bilateral frontal lobes and right somatomotor-sensory cortex. Cortical thinning is correlated to connectivity (measured functionally or structurally) to a "disease reservoir" evaluated by MRI at baseline. The atrophy pattern in the ventral frontal lobes resembles one described in certain cases of Alzheimer's disease. Our findings suggest that disease propagation to the cortex in PD follows neuronal connectivity and that disease spread to the cortex may herald the onset of cognitive impairment.

Impaired fornix-hippocampus integrity is linked to peripheral glutathione peroxidase in early psychosis.

Several lines of evidence implicate the fornix-hippocampus circuit in schizophrenia. In early-phase psychosis, this circuit has not been extensively investigated and the underlying mechanisms affecting the circuit are unknown. The hippocampus and fornix are vulnerable to oxidative stress at peripuberty in a glutathione (GSH)-deficient animal model. The purposes of the current study were to assess the integrity of the fornix-hippocampus circuit in early-psychosis patients (EP), and to study its relationship with peripheral redox markers. Diffusion spectrum imaging and T1-weighted magnetic resonance imaging (MRI) were used to assess the fornix and hippocampus in 42 EP patients compared with 42 gender- and age-matched healthy controls. Generalized fractional anisotropy (gFA) and volumetric properties were used to measure fornix and hippocampal integrity, respectively. Correlation analysis was used to quantify the relationship of gFA in the fornix and hippocampal volume, with blood GSH levels and glutathione peroxidase (GPx) activity. Patients compared with controls exhibited lower gFA in the fornix as well as smaller volume in the hippocampus. In EP, but not in controls, smaller hippocampal volume was associated with high GPx activity. Disruption of the fornix-hippocampus circuit is already present in the early stages of psychosis. Higher blood GPx activity is associated with smaller hippocampal volume, which may support a role of oxidative stress in disease mechanisms.

Glutathione deficit impairs myelin maturation: relevance for white matter integrity in schizophrenia patients.

Schizophrenia pathophysiology implies both abnormal redox control and dysconnectivity of the prefrontal cortex, partly related to oligodendrocyte and myelin impairments. As oligodendrocytes are highly vulnerable to altered redox state, we investigated the interplay between glutathione and myelin. In control subjects, multimodal brain imaging revealed a positive association between medial prefrontal glutathione levels and both white matter integrity and resting-state functional connectivity along the cingulum bundle. In early psychosis patients, only white matter integrity was correlated with glutathione levels. On the other side, in the prefrontal cortex of peripubertal mice with genetically impaired glutathione synthesis, mature oligodendrocyte numbers, as well as myelin markers, were decreased. At the molecular levels, under glutathione-deficit conditions induced by short hairpin RNA targeting the key glutathione synthesis enzyme, oligodendrocyte progenitors showed a decreased proliferation mediated by an upregulation of Fyn kinase activity, reversed by either the antioxidant N-acetylcysteine or Fyn kinase inhibitors. In addition, oligodendrocyte maturation was impaired. Interestingly, the regulation of Fyn mRNA and protein expression was also impaired in fibroblasts of patients deficient in glutathione synthesis. Thus, glutathione and redox regulation have a critical role in myelination processes and white matter maturation in the prefrontal cortex of rodent and human, a mechanism potentially disrupted in schizophrenia.

Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy.

Mechanical properties of the adventitia are largely determined by the organization of collagen fibers. Measurements on the waviness and orientation of collagen, particularly at the zero-stress state, are necessary to relate the structural organization of collagen to the mechanical response of the adventitia. Using the fluorescence collagen marker CNA38-OG488 and confocal laser scanning microscopy, we imaged collagen fibers in the adventitia of rabbit common carotid arteries ex vivo. The arteries were cut open along their longitudinal axes to get the zero-stress state. We used semi-manual and automatic techniques to measure parameters related to the waviness and orientation of fibers. Our results showed that the straightness parameter (defined as the ratio between the distances of endpoints of a fiber to its length) was distributed with a beta distribution (mean value 0.72, variance 0.028) and did not depend on the mean angle orientation of fibers. Local angular density distributions revealed four axially symmetric families of fibers with mean directions of 0°, 90°, 43° and -43°, with respect to the axial direction of the artery, and corresponding circular standard deviations of 40°, 47°, 37° and 37°. The distribution of local orientations was shifted to the circumferential direction when measured in arteries at the zero-load state (intact), as compared to arteries at the zero-stress state (cut-open). Information on collagen fiber waviness and orientation, such as obtained in this study, could be used to develop structural models of the adventitia, providing better means for analyzing and understanding the mechanical properties of vascular wall.

XuvTools: free, fast and reliable stitching of large 3D datasets.

Current biomedical research increasingly requires imaging large and thick 3D structures at high resolution. Prominent examples are the tracking of fine filaments over long distances in brain slices, or the localization of gene expression or cell migration in whole animals like Caenorhabditis elegans or zebrafish. To obtain both high resolution and a large field of view (FOV), a combination of multiple recordings ('tiles') is one of the options. Although hardware solutions exist for fast and reproducible acquisition of multiple 3D tiles, generic software solutions are missing to assemble ('stitch') these tiles quickly and accurately. In this paper, we present a framework that achieves fully automated recombination of tiles recorded at arbitrary positions in 3D space, as long as some small overlap between tiles is provided. A fully automated 3D correlation between all tiles is achieved such that no manual interaction or prior knowledge about tile positions is needed. We use (1) phase-only correlation in a multi-scale approach to estimate the coarse positions, (2) normalized cross-correlation of small patches extracted at salient points to obtain the precise matches, (3) find the globally optimal placement for all tiles by a singular value decomposition and (4) accomplish a nearly seamless stitching by a bleaching correction at the tile borders. If the dataset contains multiple channels, all channels are used to obtain the best matches between tiles. For speedup we employ a heuristic method to prune unneeded correlations, and compute all correlations via the fast Fourier transform (FFT), thereby achieving very good runtime performance. We demonstrate the successful application of the proposed framework to a wide range of different datasets from whole zebrafish embryos and C. elegans, mouse and rat brain slices and fine plant hairs (trichome). Further, we compare our stitching results to those of other commercially and freely available software solutions. The algorithms presented are being made available freely as an open source toolset 'XuvTools' at the corresponding author's website (http://lmb.informatik.uni-freiburg.de/people/ronneber), licensed under the GNU General Public License (GPL) v2. Binaries are provided for Linux and Microsoft Windows. The toolset is written in templated C++, such that it can operate on datasets with any bit-depth. Due to the consequent use of 64bit addressing, stacks of arbitrary size (i.e. larger than 4 GB) can be stitched. The runtime on a standard desktop computer is in the range of a few minutes. A user friendly interface for advanced manual interaction and visualization is also available.

[Anastomotic fistulas after colorectal resection for carcinoma: incidence and treatment in our recent experience]. / Le fistole anastomotiche dopo resezioni coliche e rettali per neoplasia. Incidenza e trattamento nella nostra esperienza recente.

AIM: The incidence of anastomotic fistula after colorectal surgery did not significantly change in the literature during the last years, despite the advances in the treatment with the use of surgical staplers. Taking into account this and other considerations, the authors present their recent experience in the surgical treatment of colorectal carcinoma, referring in particular to anastomotic fistula, related postoperative mortality and results of consequent reoperations. METHODS: From January 1, 2002 to December 31, 2005, 448 patients affected with colorectal cancer were operated on at the Surgical Department of Valduce Hospital in Como, and in 373 cases an anastomosis was performed, subdivided as follows: 144 ileocolic (38.6%), 10 ileorectal (2.7%), 219 colocolic or colorectal (58.7%). RESULTS: Twenty-five out of 373 anastomotic leaks developed (6.7%). In 9 cases (36%), the fistulas spontaneously closed with conservative treatment, while in 16 (64%) reoperation was necessary. With reference to the anatomical site, the leak occurred in 9 out of 144 patients submitted to right hemicolectomy (6.3%), in 14 out of 219 patients after left hemicolectomy or anterior resection of the rectum (6.4%) and in 2 out of 10 patients (20%) after total colectomy. The following is a detailed report of the therapeutic choices adopted by the authors. Four out of 16 reoperated patients (25%) died postoperatively from infective complications related to the fistula, while the total postoperative mortality was 2.2% (10/448). Therefore, anastomotic dehiscence was responsible for 40% of all postoperative deaths. CONCLUSIONS: Among all the different operative choices, the authors give their preference to the direct suture of the fistula and loop ileostomy, which they consider the best available choice. The subsequent operation of ileostomy closure is easier for the surgeon to perform and for the patient to withstand than colostomy closure, particularly after Hartmann's operation.

[Submucosal jejunal lymphangioma: an unusual case with obscure gastrointestinal bleeding in an adult, detected by video-capsule endoscopy and treated by laparoscopy]. / Linfangioma sottomucoso del digiuno: un raro caso di sanguinamento digestivo occulto nell'adulto, diagnosticato con video-capsula endoscopia e trattato con tecnica laparoscopica.

A 54 year-old man, without any remarkable medical history, was examined for recurrent episodes of colicky abdominal pain, over a period of nine months, with positive faecal occult blood test. Three months earlier he had undergone an extensive evaluation for a single episode of melaena, including upper gastrointestinal endoscopy, colonoscopy to the caecum, enteroscopy and an abdominal ultrasound scan, that were negative. He was then submitted to the video capsule endoscopy (Given Imaging Ltd, Yoqneam, Israel) that revealed a polypoid white-yellowish lesion in the mid portion of the jejunum. The patient was admitted to our Department of Surgery in January 2005. During the operation, performed by laparoscopic video-assisted approach, the lesion, measuring 1.5x2 cm, was found at about 100 cm from the ligament of Treitz and was successfully excised. At histology, the final diagnosis was submucosal lymphangioma. The lymphangioma is a benign neoplastic lesion of the lymphatic system that usually is present in infancy and is found, in the majority of the patients, in the subcutaneous tissue outside the abdomen. The intrabdominal site accounts for less than 1% of the cases, and often occurs in the mesentery of the small bowel. Finding the lesion in the submucosa of the jejunum in an adult is very rare. The case here reported seems unusual to the Authors and worthy of publication because of the chronic, ambiguous clinical symptomatology, the occult digestive blood loss, and all the diagnostic examinations resulting negative, except for the video-capsule endoscopy. Moreover, the choice of the laparoscopic video-assisted technique, confirming the expected site of the lesion, with a ''minimal'' small bowel resection, made the postoperative course of the patient very short and uneventful. He is well and free of disease one year after the intervention. From a brief review of surgical literature, the case reported is the second one detected by the video capsule endoscopy and the fifth operated on by laparoscopy.

[Colon recanalization after Hartmann's procedure. A challenge for the surgeon or a strategy to be changed?]. / La ricanalizzazione del colon dopo l'intervento di Hartmann. Un impegno per il chirurgo o una strategia da cambiare?

AIM: Restoration of colorectal continuity is the second step of the procedure originally described by H. Hartmann for the treatment of sigmoid colon cancers. It is a safe, but complex procedure, that needs a meticulous surgical technique and is associated with a significant morbidity in as many as 40% of cases. For this reason, many patients are not submitted to reversal of the colostomy. METHODS: The authors report their experience: 32 patients underwent colostomy closure after Hartmann's procedure during the last 8 years. RESULTS: The mortality rate was nil, but post-operative complications occurred in 12 patients (37.5%), namely: wound infection (11 patients) and anastomotic leak (2 patients). CONCLUSION: In light of this, it could be wiser to perform, in the patients affected with benign pathology, and in those affected with limited malignant pathology (T3), resection of the diseased segment of colon and primary anastomosis with temporary ileostomy, reserving Hartmann's procedure to patients unsuitable to one step treatment because of their poor general and local conditions.