AB5 Enterotoxin-Mediated Pathogenesis: Perspectives Gleaned from Shiga Toxins

Foodborne diseases affect an estimated 600 million people worldwide annually, with the majority of these illnesses caused by Norovirus, Vibrio, Listeria, Campylobacter, Salmonella, and Escherichia coli. To elicit infections in humans, bacterial pathogens express a combination of virulence factors and toxins. AB5 toxins are an example of such toxins that can cause various clinical manifestations, including dehydration, diarrhea, kidney damage, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Treatment of most bacterial foodborne illnesses consists of fluid replacement and antibiotics. However, antibiotics are not recommended for infections caused by Shiga toxin-producing E. coli (STEC) because of the increased risk of HUS development, although there are conflicting views and results in this regard. Lack of effective treatment strategies for STEC infections pose a public health threat during outbreaks; therefore, the debate on antibiotic use for STEC infections could be further explored, along with investigations into antibiotic alternatives. The overall goal of this review is to provide a succinct summary on the mechanisms of action and the pathogenesis of AB5 and related toxins, as expressed by bacterial foodborne pathogens, with a primary focus on Shiga toxins (Stx). The role of Stx in human STEC disease, detection methodologies, and available treatment options are also briefly discussed.

An update on the ophthalmic features in hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)

Hereditary haemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber syndrome is a rare autosomal dominant disease, characterised by systemic angiodysplasia. Dysfunction of the signalling pathway of β transforming growth factor is the main cause of HHT principally owing to mutations of the genes encoding for endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1). Clinical manifestations can range from mucocutaneous telangiectasia to organ arterio-venous malformations and recurrent epistaxis. The early clinical manifestations may sometimes be subtle, and diagnosis may be delayed. The main ophthalmic manifestations historically reported in HHT are haemorrhagic epiphora, and conjunctival telangiectasia present in 45–65% of cases, however, imaging with wide-field fluorescein angiography has recently shown peripheral retinal telangiectasia in 83% of patients. Optimal management of HHT requires both understanding of the clinical presentations and detection of early signs of disease. Advances in imaging methods in ophthalmology such as wide-field fluorescein angiography, spectral domain optical coherence tomography, and near infrared reflectance promise further insight into the ophthalmic signs of HHT towards improved diagnosis and early management of possible severe complications.

Research Trends and Hotspots of Q Fever Research: A Bibliometric Analysis 1990-2019

Q fever is a worldwide distributed zoonosis caused by Coxiella burnetii, a Gram-negative bacterium. Despite existence of large amount of research data on the developments related to Q fever, no bibliometric analysis of this subject is available to our knowledge. Bibliometric studies are an essential resource to track scholarly trends and research output in a subject. This study is aimed at reporting a bibliometric analysis of publications related to Q fever (2,840 articles published in the period 1990-2019) retrieved from Science Citation Index Expanded, an online database of Clarivate Analytics Web of Science Core Collection. Data was retrieved using keywords “Q fever” or “Coxiella burnetii” in title, abstract, and author keywords to describe important research indicators such as the kind and language of articles, the most important publications, research journals and categories, authors, institutions, and the countries having the most significant contribution to this subject. Finally, the emerging areas in field of diagnosis, host range, and clinical presentation were identified. Word cluster analysis of research related to Q fever revealed that major focus of research has been on zoonosis, seroprevalence, laboratory diagnosis (mainly using ELISA and PCR), clinical manifestations (abortion and endocarditis), vectors (ticks), and hosts (sheep, goat, and cattle). This bibliometric study is intended to visualize the existing research landscape and future trends in Q fever to assist in future knowledge exchange and research collaborations.

Selective IgA Deficiency and Allergy: A Fresh Look to an Old Story

Selective IgA deficiency (SIgAD) is the most common human primary immune deficiency (PID). It is classified as a humoral PID characterized by isolated deficiency of IgA (less than 7 mg/dL but normal serum IgG and IgM) in subjects greater than 4 years of age. Intrinsic defects in the maturation of B cells and a perturbation of Th cells and/or cytokine signals have been hypothesized to contribute to SIgAD pathogenesis. The genetic basis of IgA deficiency remains to be clarified. Patients with SIgAD can be either asymptomatic or symptomatic with clinical manifestations including allergy, autoimmunity and recurrent infections mainly of the respiratory and gastrointestinal tract. Studies analyzing allergy on SIgAD patients showed prevalence up to 84%, supporting in most cases the relationship between sIgAD and allergic disease. However, the prevalence of allergic disorders may be influenced by various factors. Thus, the question of whether allergy is more common in SIgAD patients compared to healthy subjects remains to be defined. Different hypotheses support an increased susceptibility to allergy in subjects with SIgAD. Recurrent infections due to loss of secretory IgA might have a role in the pathogenesis of allergy, and vice versa. Perturbation of microbiota also plays a role. The aim of this review is to examine the association between SIgAD and atopic disease and to update readers on advances over time at this important interface between allergy and SIgAD.

An experience with Foot Macrodactyly: A case report and review of literature

Macrodactyly is a rare congenital malformation with clinical manifestations such as enlargement of soft tissue and osseous elements. It causes various health issues such as pain, difficulty in wearing shoes, impairment in ambulatory ability and gait development, aesthetic problem, and psychological issues. The aetiology of macrodactyly is ambiguous; however, its association with PIK3CA /AKT1 genes has been reported recently. In the present study, a rare congenital macrodactyly of second and third toe of right foot along with deformed leg in 16-year-old girl has been reported. A progressive increase in the size of the second and third toe of the right foot and deformed reddish swollen area on the same lower leg below knee was seen in the patient. The malformation was present at the time of birth and at the age of one year the patient was operated for macrodactyly, but again the toe progressively increased to the previous size. She was presented with multiple health problems. There was no positive family history and/or other congenital malformation. Thus, it was suggested that due to variable phenotypic manifestations, appropriate treatment should be chosen for the patient individually.

Sexual Dysfunction in Chronically Medicated Male Inpatients With Schizophrenia: Prevalence, Risk Factors, Clinical Manifestations, and Response to Sexual Arousal

BackgroundSexual dysfunction is a common symptom in patients with schizophrenia, especially in chronically medicated patients. However, the relationship between sexual dysfunction and emotional response to sexual arousal in male patients with schizophrenia remains unclear. This study aimed to assess the incidence, risk factors of sexual dysfunction in males, and their clinical correlations to sexual arousal in male patients with schizophrenia in China.MethodsA total of 162 male patients, aged 18–50 years, with schizophrenia were recruited from a psychiatric hospital in Ganzhou. The clinical symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). The Arizona Sexual Experience Scale was utilized to evaluate sexual dysfunction. Erotic images were selected from International Affective Picture System (IAPS). Sixty-eight out of the 162 subjects completed the erotic pictures reactivity task.ResultsOverall, 48 (29.6%) patients were measured as having global sexual dysfunction, 72 (44.4%) patients as having strength of sex drive dysfunction, 51 (31.5%) patients as having sexual arousal dysfunction, 55 (34.0%) patients as having penile erection dysfunction, 60 (37.0%) patients as having reached orgasm dysfunction, and 60 (37.0%) patients as having satisfaction with orgasm dysfunction. The sexual dysfunction patients had significantly higher scores on the negative symptoms of the PANSS. The only important predictor of sexual dysfunction was the severity of PANSS negative factor. The sense of pleasure and arousal post viewing erotic images in the sexual dysfunction group were lower compared to the non-sexual dysfunction group. The sense of pleasure and approach motivation were significantly negatively correlated with the severity of sexual dysfunction.ConclusionsThis study shows that nearly one-third of young and middle-aged chronically medicated male inpatients with schizophrenia suffer from sexual dysfunction. The negative factor of the PANSS can be regarded as the risk factor of sexual dysfunction. Schizophrenia patients with sexual dysfunction experienced lower pleasure and higher avoidance motivation than non-sexual dysfunction patients when exposed to erotic stimuli.

Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.

Cranio-Mandibular Disorders after Whiplash Injury: A Mono-Institutional Clinical Study on 31 Patients

Background: Whiplash is a consequence of traumatic injuries, mostly related to road accidents, with variable clinical manifestations, also known as Whiplash Associated Disorders, such as neck, head and temporo-cranio-mandibular pain. Methods: The current study aims to evaluate the onset and evolution of temporomandibular joint pain in people with whiplash in a study group treated with the use of Zimmer Collars (adjustable rigid cervical collars for neck immobilization), as compared to a control group. This prospective study included 31 patients followed by the Dental Prosthesis Department of the University of Bari “Aldo Moro”: 20 patients with whiplash (age range: 20–39 years) treated with Zimmer collars and 11 patients with whiplash (age range: 20–33 years) who were not. Immediately after the whiplash occurred, a visual analogue scale (VAS) was used to describe the intensity of pain and to complete the chart of the European Academy of Craniomandibular Disorders. Five out of twenty patients, already treated with a Zimmer collar, wore an occlusal splint as well because of persistent pain reported at the 28-day and 60-day follow-up and were supported by pharmacological therapy with analgesics (paracetamol) and muscle relaxants (thiocolchicoside). Results: During the last follow-up (at six months), three out of five patients displayed a residual VAS score of 3, 4, and 5, respectively, while the remaining two displayed a VAS of 0. In the control group, four out of eleven patients needed to wear an occlusal splint but without muscle relaxants and analgesics pharmacological therapy; these four corresponded to the patients showing a residual painful symptomatology, with VAS reaching value of 2, and also were the oldest patients of the group. Data regarding VAS values and Zimmer collar use, both at the first visit and six months later, were statistically analyzed. Conclusion: Our prospective study highlights how whiplash-associated acute disorders are often self-limiting over a period of few months, thus reducing the possibility of symptom chronicity; the latter seems to be strictly related to lesion severity, pre-existence of a craniomandibular dysfunction and patient age, but appears to be independent from Zimmer collar use, as statistically confirmed.

Significant Stenosis of the Brachiocephalic Trunk and Moderate Stenosis of the Left Circumflex Artery in Computed Tomography Angiography Images

Atherosclerosis, as a civilization disease, is a serious epidemiological problem. Significant carotid disease and significant coronary artery disease result in acute consequences, such as ischemic stroke and myocardial infarction, which are the major causes of cardiovascular mortality. Typically, atherosclerosis of the aortic arch branches involves the bulbs of the common carotid arteries and the proximal segments of the internal carotid arteries, and can be effectively assessed by ultrasonography. Computed tomography angiography enables the identification of patients with less typical clinical manifestations of atherosclerosis, e.g., brachiocephalic trunk stenosis with symptoms of the steal syndrome and moderate stenosis in the coronary arteries. We present examples of computed tomography angiography images of this type of changes.

Single-Cell Transcriptome Profiling Unravels Distinct Peripheral Blood Immune Cell Signatures of RRMS and MOG Antibody-Associated Disease

Relapsing-remitting multiple sclerosis (RRMS) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) are inflammatory demyelinating diseases of the central nervous system (CNS). Due to the shared clinical manifestations, detection of disease-specific serum antibody of the two diseases is currently considered as the gold standard for the diagnosis; however, the serum antibody levels are unpredictable during different stages of the two diseases. Herein, peripheral blood single-cell transcriptome was used to unveil distinct immune cell signatures of the two diseases, with the aim to provide predictive discrimination. Single-cell RNA sequencing (scRNA-seq) was conducted on the peripheral blood from three subjects, i.e., one patient with RRMS, one patient with MOGAD, and one patient with healthy control. The results showed that the CD19+ CXCR4+ naive B cell subsets were significantly expanded in both RRMS and MOGAD, which was verified by flow cytometry. More importantly, RRMS single-cell transcriptomic was characterized by increased naive CD8+ T cells and cytotoxic memory-like Natural Killer (NK) cells, together with decreased inflammatory monocytes, whereas MOGAD exhibited increased inflammatory monocytes and cytotoxic CD8 effector T cells, coupled with decreased plasma cells and memory B cells. Collectively, our findings indicate that the two diseases exhibit distinct immune cell signatures, which allows for highly predictive discrimination of the two diseases and paves a novel avenue for diagnosis and therapy of neuroinflammatory diseases.