Staying tuned for post-COVID-19 syndrome: looking for new research to sniff out.

Post-COVID-19 syndrome was defined as a persistent and protracted illness, which follows acute COVID-19 infection. This condition continues for more than 12 weeks and cannot be attributed to other clinical situations. Researchers and clinicians are allied in unraveling the molecular pathogenetic mechanisms and the clinical development of this unexpected SARS-CoV-2 infectious evolution. Anosmia, dysgeusia, fatigue, dyspnea, and 'brain fog' are common symptoms observed in the Post-COVID-19 syndrome, depicting a multiorgan involvement associated with injuries involving mainly cardiovascular, pulmonary, musculoskeletal, and neuropsychiatric systems. This commentary analyzes the state of the art of Post-COVID-19 interdisciplinary studies, confirming that we are facing a truly intricate biomedicine story.

Early reperfusion injury is associated to MMP2 and IL-1ß elevation in cortical neurons of rats subjected to middle cerebral artery occlusion.

The pathophysiological processes implicated in ischemic brain damage are strongly affected by an inflammatory reaction characterized by activation of immune cells and release of soluble mediators, including cytokines and chemokines. The pro-inflammatory cytokine interleukin (IL)-1ß has been implicated in ischemic brain injury, however, to date, the mechanisms involved in the maturation of this cytokine in the ischemic brain have not been completely elucidated. We have previously suggested that matrix metalloproteinases (MMPs) may be implicated in cytokine production under pathological conditions. Here, we demonstrate that significant elevation of IL-1ß occurs in the cortex as early as 1h after the beginning of reperfusion in rats subjected to 2-h middle cerebral artery occlusion (MCAo). At this early stage, we observe increased expression of IL-1ß in pericallosal astroglial cells and in cortical neurons and this latter signal colocalizes with elevated gelatinolytic activity. By gel zymography, we demonstrate that the increased gelatinolytic signal at 1-h reperfusion is mainly ascribed to MMP2. Thus, MMP2 seems to contribute to early brain elevation of IL-ß after transient ischemia and this mechanism may promote damage since pharmacological inhibition of gelatinases by the selective MMP2/MMP9 inhibitor V provides neuroprotection in rats subjected to transient MCAo.

Understanding the multifaceted role of inflammatory mediators in ischemic stroke.

The evolution of ischemic brain damage is strongly affected by an inflammatory reaction that involves soluble mediators, such as cytokines and chemokines, and specialized cells activated locally or recruited from the periphery. The immune system affects all phases of the ischemic cascade, from the acute intravascular reaction due to blood flow disruption, to the development of brain tissue damage, repair and regeneration. Increased endothelial expression of adhesion molecules and blood-brain barrier breakdown promotes extravasation and brain recruitment of blood-borne cells, including macrophages, neutrophils, dendritic cells and T lymphocytes, as demonstrated both in animal models and in human stroke. Nevertheless, most anti-inflammatory approaches showing promising results in experimental stroke models failed in the clinical setting. The lack of translation may reside in the redundancy of most inflammatory mediators, exerting both detrimental and beneficial functions. Thus, this review is aimed at providing a better understanding of the dualistic role played by each component of the inflammatory/immune response in relation to the spatio-temporal evolution of ischemic stroke injury.

Modeling socially anhedonic syndromes: genetic and pharmacological manipulation of opioid neurotransmission in mice.

Social anhedonia, or the diminished capacity to experience pleasure and reward from social affiliation, is a major symptom of different psychiatric disorders, including some forms of infantile autism and schizophrenia spectrum disorders. The brain opioid hypothesis of social attachment is a promising model for achieving insights into how neurobiological and developmental factors contribute to the regulation of social reward. In this study, genetic knocking-out and naltrexone (NTRX) treatment during the first 4 days of life were used to disrupt opioid neurotransmission in mouse pups and their attachment relationships with the mother. Both permanent (genetic) and transient (pharmacological) manipulations of opioid neurotransmission exerted long-term effects on social affiliation. When juveniles, both µ-opioid receptor knockout mice and NTRX-treated pups showed reduced interest in peers and no preference for socially rewarding environment. These results demonstrate that sociability in juvenile mice is highly dependent on the establishment during infancy of a positive affective relationship with their mothers and that opioid neurotransmission has a major role in the regulation of social hedonic capacity. If the validity of this animal model will be confirmed by future research, translational studies focusing on the interaction between early experience and opioid neurotransmission could provide useful insights for identifying endophenotypes of human psychiatric disorders associated with social anhedonia.

Angiomegaly and arterial aneurysms.

Angiomegaly is characterized by an alteration in the elastic component of arterial and venous vessels determining their elongation and tortuousness. This involves an increased risk of thromboembolism and aneurysmal degeneration in affected subjects, even if they have been asymptomatic for a long time. The aim of this study is to demonstrate the correlation between angiomegaly and aneurysmal disease. A total of 163 patients suffering from a peripheral arterial aneurysm were included, 74 of these with an iliac aneurysm, 41 with a femoral aneurysm and 48 suffering from popliteal aneurysm. All patients were examined by color Doppler ultrasonography (CDU) and angio-CT with contrast medium. Eighteen cases of arteriomegaly were diagnosed, and the prevalence in the examined population was 11%. This study demonstrates the close association existing between aneurysms in peripheral arteries and arteriomegaly. Peripheral arterial aneurysms in association with arteriomegaly involve an increased risk of complications like thrombosis, embolism and rupture. The showed familiarity in the arteriomegaly incidence leads to predisposition of screening programs, using CDU, among relatives of patients affected by arteriomegaly and/or peripheral arterial aneurysms.

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference.

BACKGROUND: Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM: The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS: Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS: The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

Che-1 activates XIAP expression in response to DNA damage.

X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis proteins family that selectively binds and inhibits caspase-3, -7 and -9. As such, XIAP is an extremely potent suppressor of apoptosis and an attractive target for cancer treatment. Che-1 is an antiapoptotic agent involved in the control of gene transcription and cell proliferation. Recently, we showed that the checkpoint kinases ATM/ATR and checkpoint kinase 2 physically and functionally interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage. These Che-1 modifications induce transcription of p53, and Che-1 depletion strongly sensitizes tumor cells to anticancer drugs. Here we show that Che-1 activates XIAP expression in response to DNA damage. This effect is mediated by Che-1 phosphorylation and requires NF-kappaB. Notably, we found that XIAP expression is necessary for antiapoptotic activity of Che-1 and that in vivo downregulation of Che-1 by small interference RNA strongly enhanced the cytotoxicity of anticancer drugs.

Blue rubber bleb nevus syndrome: manifestations at computed tomography.

Blue rubber bleb nevus syndrome (BRBNS) is a rare condition that consists of multiple venous malformations involving several organ systems, particularly the skin and the gastrointestinal tract, but any part of the body may be affected. Less than 250 cases have been reported in the literature. The authors describe the thoracic, abdominal, and pelvic imaging characteristics at computed tomography (CT) in a 50-year-old man with BRBNS.

High prevalence of hyperplastic colonic polyps in acromegalic subjects.

We evaluated the prevalence and features of colonic polyps in a population of acromegalic subjects, compared to a control group of patients with irritable bowel syndrome (IBS). Colonic polyps were found in 30 acromegalic subjects (40%) and in 10 controls (13%) (P < 0.0001). Among the acromegalic patients, polyps were of the hyperplastic type in 27 subjects (90%) and adenomatous in 3 (10%). In the control group, polyps were hyperplastic in nine subjects (90%) and adenomatous in one (10%). We also observed a significant association (P < 0.0001) between the presence of hyperplastic polyps and the older age in both the acromegalic and the control groups. There were no differences between the two groups regarding sex, site, size, or macroscopic and histological types of polyps. Acromegalic patients have a higher prevalence of colonic hyperplastic polyps than IBS subjects, while the prevalence of adenomatous polyps is similar in the two groups.

Mortality in patients with coeliac disease and their relatives: a cohort study.

BACKGROUND: Although previous studies have shown increased mortality in patients with coeliac disease and their relatives, no data are available in relation to different patterns of clinical presentation. We assessed mortality in patients with coeliac disease and their first-degree relatives. METHODS: We enrolled, in a prospective cohort study, 1072 adult patients with coeliac disease consecutively diagnosed in 11 gastroenterology units between 1962 and 1994, and their 3384 first-degree relatives. We compared the number of deaths up to 1998 with expected deaths and expressed the comparison as standardised mortality ratio (SMR) and relative survival ratio. FINDINGS: 53 coeliac patients died compared with 25.9 expected deaths (SMR 2.0 [95% CI 1.5-2.7]). A significant excess of mortality was evident during the first 3 years after diagnosis of coeliac disease and in patients who presented with malabsorption symptoms (2.5 [1.8-3.4]), but not in those diagnosed because of minor symptoms (1.1 [0.5-2.2]) or because of antibody screening (1.2 [0.1-7.0]). SMR increased with increasing delay in diagnosis and for patients with poor compliance with gluten-free diet. Non-Hodgkin lymphoma was the main cause of death. No excess of deaths was recorded in relatives with coeliac disease. INTERPRETATION: Prompt and strict dietary treatment decreases mortality in coeliac patients. Prospective studies are needed to clarify the progression of mild or symptomless coeliac disease and its relation to intestinal lymphoma.

Prevalence and early diagnosis of coeliac disease in autoimmune thyroid disorders.

BACKGROUND AND AIMS: Coeliac disease is associated with several autoimmune disorders such as insulin-dependent diabetes, Sjogren's syndrome, Addison's disease and thyroid diseases. The aim of our study was to evaluate the prevalence of coeliac disease in patients affected by autoimmune thyroid diseases by means of anti-gliadin and anti-endomysial antibodies. PATIENTS: We studied 92 patients affected by autoimmune thyroid diseases (47 chronic autoimmune thyroiditis, 22 Hashimoto's thyroiditis and 23 Graves' disease). Ninety patients with non autoimmune thyroid disorders (51 multifollicular goitre, 28 solitary nodule and 11 papillary carcinoma) and 236 blood donors also took part in the study as control groups. METHODS: Total serum IgA were measured in all subjects to exclude selective IgA deficiency; then we measured anti-gliadin antibodies and anti-endomysial antibodies. In patients with anti-gliadin/anti-endomysial antibody positivity and/or with haematinic and laboratory signs of malabsorption we carried out gastrointestinal endoscopy with duodenal histological examination. RESULTS: Among the 92 patients with autoimmune thyroid disease, 4 (4.3%) showed anti-gliadin and anti-endomysial positivity and had coeliac disease; among the 90 patients with non autoimmune thyroid diseases, 1 (1.1%) had coeliac disease; finally, among the blood donors, 1 subject (0.4%) was anti-gliadin-anti-endomysium antibody positive and had coeliac disease. Those subjects presenting with only anti-gliadin antibody positivity did not have coeliac disease. CONCLUSIONS: These results show that the prevalence of coeliac disease in patients with autoimmune thyroid diseases is significantly increased when compared with the general population (p = 0.009) but not with patients affected by non autoimmune thyroid disorders (p = 0.18). We suggest a serological screening for coeliac disease in all patients with autoimmune thyroid disease measuring anti-endomysial antibodies, considering that early detection and treatment of coeliac disease are effective in preventing its complications.

Effect of moderate and heavy alcohol consumption on intestinal transit time.

BACKGROUND: Alcohol abusers frequently have gastrointestinal symptoms, such as diarrhea, nausea and vomiting. In the genesis of these symptoms multiple mechanisms are involved, including alteration of gastrointestinal motility. The aim of our study was to investigate oro-cecal transit time (OCTT) using the H2-breath test (H2-BT) in moderate and heavy drinkers. MATERIALS AND METHODS: We studied 40 chronic drinkers: 20 with heavy alcohol consumption (> or = 60 g/day for men and > or = 40 g/day for women) and 20 with moderate alcohol intake (< 60 g/day for men and < 40 g/day for women). The control group consisted of 20 teetotal subjects. All subjects underwent a lactulose H2-BT to assess OCTT. RESULTS: OCTT in heavy alcohol drinkers ranged from 100 to 240 min, with a mean of 149.5 min, while OCTT in moderate drinkers ranged from 70 to 140 min, with a mean of 109 min. In the control group the mean OCTT was 100 mins, ranging from 70 to 130 min. The difference between alcohol abusers and controls was statistically significant; on the contrary, there was no statistically significant difference between moderate alcohol drinkers and teetotallers. CONCLUSIONS: Our study shows that only in chronic heavy alcohol drinkers is OCTT clearly increased. Multiple mechanisms are hypothesized to explain motility disorder, such as visceral autonomic neuropathy, inflammation and loss of contractile proteins of smooth muscle layer of the small intestine.

Histologic types and surveillance of gastric polyps: a seven year clinico-pathological study.

BACKGROUND/AIMS: This is a seven-year prospective study based on all gastroscopic examinations of our patient population in order to study gastric polyps. METHODOLOGY: One hundred and twenty-one polyps, removed from 96 patients were analysed. All polyps, after endoscopic polypectomy, were classified according to their histotype. The follow-up was carried out in 49 patients for a mean time of 40 months. RESULTS: Polypoid lesions were more frequent in females (57.3%) and they were preferentially located in antrum (60.3%). Hyperplastic and inflammatory polyps were 55.4% and 28.9%, respectively, while adenomatous lesions were 9.9%. Four fundic gland polyps, 1 carcinoid, 1 type I early gastric cancer and 1 pancreatic heterotopia were also found. During the follow-up no malignant lesion was encountered. On the other hand 25 benign polyps were found in 19 patients. CONCLUSIONS: Our experience confirms that there is a close relationship between the size of the polyps and the neoplastic change. In fact, in our series all polyps were smaller than 2 cm and only one malignancy was found (an early gastric cancer). None of adenomatous polyps was associated with gastric adenocarcinoma. Our data also indicates that when a polypectomy is carried out for small polyps (smaller than 2 cm.) a strict follow-up is necessary for the neoplastic polyps only.

Disappearance of gastric mucosa-associated lymphoid tissue in coeliac patients after gluten withdrawal.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) develops in gastric mucosa in response to chronic antigenic stimulation, such as Helicobacter pylori infection. However, reactive lymphoid follicles have been found also in the stomach of H. pylori-negative coeliac patients, suggesting that other environmental factors may be involved in MALT genesis. The aim of our study was to evaluate the effects of gluten withdrawal in H. pylori-negative coeliac patients with gastric MALT. METHODS: We studied 23 H. pylori-negative untreated coeliac patients with gastric MALT. All patients underwent determination of antigliadin (AGA) and antiendomysium antibodies (EMA) and upper endoscopy with multiple biopsies in duodenum, gastric corpus, and antrum. Lymphoid follicles and H. pylori status were assessed by histopathologic and enzymatic analysis. All patients were started on a gluten-free diet and were reevaluated after 12 months. To consider their adherence to the gluten-free diet we relied on direct patient questioning. Thirteen patients who had strictly adhered to the gluten-free diet constituted our study group. Ten patients who had not strictly adhered to gluten withdrawal from their diet constituted the control group. RESULTS: Regression of MALT was obtained in 9 of 13 (69%) patients who strictly followed the gluten-free diet; in the control group MALT disappeared in 2 of 10 (20%) patients (P=0.0361). DISCUSSION: Disappearance of reactive lymphoid follicles in the gastric mucosa of H. pylori-negative coeliac patients after gluten withdrawal suggests that antigens related to alimentary gluten may constitute persistent stimuli for development of gastric MALT in coeliac patients.

Influence of alcohol on gastrointestinal motility: lactulose breath hydrogen testing in orocecal transit time in chronic alcoholics, social drinkers and teetotaler subjects.

BACKGROUND/AIMS: The gastrointestinal tract is directly affected by the ingestion of alcohol. While the effect of acute ingestion of alcohol on the motility of the small intestine is well known, the influence of chronic intake of moderate amounts of alcohol and chronic alcoholism on gastrointestinal motility remains poorly understood. The aim of this study was to examine the orocecal transit (OCt) times in patients with chronic alcoholism and in "social drinkers" and compare them with a group of healthy teetotaler subjects, to assess the effects of chronic aleohol consumption on gastrointestinal transit through the application of a non-invasive technique: the hydrogen breath test. METHODOLOGY: Thirty-one alcoholics were enrolled in the study. The control groups consisted of 31 healthy social drinkers and 24 healthy teetotaler subjects. OCt time was assessed using the hydrogen breath test after the administration of 10 g of lactulose. RESULTS: The OCt time in patients with alcoholism was significantly delayed as compared with the social drinkers (p < 0.001) and healthy teetotaler subjects (p < 0.001); the OCt time in social drinkers was significantly longer than in healthy teetotaler subjects (p < 0.05). In the alcoholic group, there was no significant correlation between the OCt time and daily alcohol intake or years of alcohol addiction. CONCLUSION: Our results show a significant prolongation of the OCt time, both in patients with alcoholism and in social drinkers, as compared to teetotaler subjects. Our findings of an increased OCt time related to the consumption of alcohol could support the hypothesis of the toxic effect of ethanol on smooth muscle contractile proteins of the small intestine and on vagal function.

Quality control study of H2 breath testing for the diagnosis of carbohydrate malabsorption in Italy. The "Tenue Club" Group.

BACKGROUND AND AIMS: H2 breath testing is increasingly used in Italy. The aim of this multicenter study was to assess the accuracy of this technique in the diagnosis of carbohydrate malabsorption. METHODS: An anonymous questionnaire was used to collect information about H2 breath testing methods and to design the quality control study. Fifteen out of 23 laboratories responded to the questionnaire and 12/23 completed the entire study. RESULTS: The survey revealed that a large variety of H2 testing methods are employed in Italy, but none have been previously tested for accuracy. This prospective study showed that these tests fail to identify > 20% of patients with malabsorption. In contrast, a new method based on single H2 breath measurement at 6 hours after lactulose ingestion and a cutoff value of greater than 5 ppm, had a sensitivity of 92% +/- 4% and a specificity of 94% +/- 0.5%. Increasing the cut-off to 10 ppm resulted in a sensitivity of 88% +/- 9% and a specificity of 100%. This improved accuracy was obtained with a much simpler testing procedure in which only one breath sample is analyzed, in contrast to the baseline and multiple subsequent samples that are analyzed using the currently employed techniques. CONCLUSIONS: A great improvement in the accuracy of the H2 breath test, as well as a considerable saving in terms of time and costs, may be possible through the use of a new, simplified H2 breath test followed by careful H2 analysis.

Effects of propylthiouracil on intestinal transit time and symptoms in hyperthyroid patients.

BACKGROUND/AIMS: Gastrointestinal disturbances such as diarrhea and malabsorption with steatorrhea may show up in hyperthyroid patients. The aim of our study was to evaluate oro-caecal transit time (OCTT) and gastrointestinal symptoms in hyperthyroid patients before and after propylthiouracil administration. MATERIALS AND METHODS: Twenty hyperthyroid patients (15 Females and 5 Males, mean age 47 years) were studied. Eight of them had diarrhea and 10 steatorrhea. The control group was composed of 20 healthy volunteers (13 F and 7 M, mean age 49 yrs). OCTT and fecal fat excretion were measured before and after propylthiouracil administration (300 mg/day for 10 day and then 200 mg/day for 30 days). RESULTS: Before the treatment in hyperthyroid patients had began the mean OCTT was significantly lower than in the control group (64 min. versus 107 min; p < 0.0001). After treatment mean OCTT became similar to the controls (p = ns); diarrhea disappeared in all affected patients and mean fecal fat excretion was reduced from 7.9 gr/24h to 3.4 gr/24h, with a statistically significantly difference (p < 0.0001). CONCLUSIONS: The treatment with propylthiouracil induces the normalization of thyroid hormone status and consequently of OCTT with the disappearance of gastrointestinal symptoms, such as diarrhea and steatorrhea, with a better efficacy if compared to other drugs utilized in the treatment of hyperthyroidism.

Clinical assessment of the relationship of Helicobacter pylori to gastroduodenal pathologies. A prospective analysis of 253 consecutive patients.

The aim of our study was to evaluate the relationship between Helicobacter pylori infection and various gastroduodenal diseases. We also took into consideration alcohol intake and smoking. Two-hundred and fifty-three consecutive patients with ulcer-like symptoms underwent gastroscopic and histological examinations. H. pylori status was evaluated by means of culture, Giemsa stain and CP-test, upon obtaining bioptic samples of gastric mucosa. Two hundred eighteen patients were affected by gastritis, 171 of which were H. pylori positive (78.4%); of 164 patients with active gastritis, 158 were H. pylori positive (96.3%). In 63 patients with duodenal ulcer, H. pylori was present in 58 cases (92.1%). Of 14 patients with gastric ulcer, 11 were H. pylori positive (78.6%). Out of 133 patients with duodenitis associated with active ulcer or a history of previous ulcer, H. pylori was found in 112 patients (84.2%). Among the 27 patients with "autonomous" duodenitis, 18 were H. pylori positive (66.6%); the comparison between the two groups of patients with duodenitis concerning H. pylori infection was statistically significant (p = 0.033). Of the 119 patients tested for acquired MALT, 39 were found positive (32.7%); among these 34 patients were H. pylori positive (87.1%) and only 5 patients were H. pylori negative (12.9%). Thus our study confirms the importance of H. pylori in gastroduodenal pathology underlining its role in the development of acquired MALT (mucosa associated lymphoid tissue) for its possible evolution in low grade B cell primary gastric lymphoma. Alcohol intake and smoking do not appear to play a role in H. pylori infection.

Parents in the operatory.

Dentists who treat children must continually evaluate methods for managing patients. Psychological, physical and pharmacotherapeutic techniques have been described, reviewed and questioned in papers and presentations throughout the history of dentistry. This evaluation is important because it provides avenues for controversy and change, leading to improved patient care. The issue of parental presence in the dental operatory continues to generate conflicting opinions and to stimulate debates among practitioners. This controversy has resulted in divergent reports in the dental literature, with practitioners receiving contrasting information and advice for managing the patient/parent unit. The purpose of this paper is to review the history and issues surrounding parental presence in the dental operatory, and to present guidelines for allowing parents to be with their children during treatment.

Events related to Epstein-Barr virus binding and superinfection of Raji cells.

Raji cells, a CR2-positive Burkitt lymphoma cell line, incubated in normal human serum, activate C3 and fix C3-derived fragments. The presence of these molecules on the cell surface does not affect subsequent Epstein-Barr virus (EBV) binding but it prevents superinfection. On the other hand, EBV superinfection is enhanced if Raji cells were incubated with heat-inactivated serum whose C3 fragments may bind only through receptor-binding sites. These results indicate that the region on cell surface offering the covalent site to C3 fragments would be essential for EBV superinfection. Incubation of Raji cells for 1 min with EBV results in the phosphorylation of CR2 and of a high-molecular-weight protein followed by their dephosphorylation, completed already after 20 min. This finding ascribes to EBV a prompt action through its receptor, different from that of other compounds causing a prolonged CR2 phosphorylation. Our data suggest that at least two binding sites are required for EBV superinfection of Raji cells or that specific patterns of CR2 phosphorylation may modulate Raji superinfection by EBV.