HIV transmission by human bite: a case report and review of the literature—implications for post-exposure prophylaxis

We report a case of a probable HIV-1 transmission by human bite. The analyzed data from ten previously reported suspected or allegedly confirmed HIV transmissions revealed a deep bleeding bite wound as the primary risk factor. A high HIV plasma viral load and bleeding oral lesions are present most of the time during HIV transmission by bite. HIV post-exposure prophylaxis (PEP) should be recommended in case of a bleeding wound resulting from a bite of an HIV-infected person. PEP was missed in this presented case

Clonal expansion of CD4+CD8+ T cells in an adult patient with Mycoplasma pneumoniae-associated Erythema multiforme majus

Background: Erythema multiforme (EM) is an acute, immune-mediated mucocutaneous disease, most often preceded by herpes simplex virus (HSV) infection or reactivation. Mycoplasma pneumoniae (Mp) is considered the second major trigger of EM and is often associated with an atypical and more severe presentation of disease, characterized by prominent mucosal involvement. However, contrary to HSV-associated Erythema multiforme (HAEM), immunological mechanisms of Mp-associated EM remain unclear. Case presentation: We present the case of a 50-year-old male patient presenting with community-acquired pneumonia (CAP) and erythema multiforme majus (EMM). Acute Mp infection was diagnosed by seroconversion, with no evidence of HSV infection as a cause of EMM. We performed immune phenotyping of blister fluid (BF) and peripheral blood (PB) T cells and detected a clonally expanded TCRV beta 2(+) T cell population that was double positive for CD4 and CD8, and expressed the cytotoxic markers granulysin and perforin. This CD4(+)CD8(+) population comprised up to 50.7% of BF T cells and 24.9% of PB T cells. Two years prior to the onset of disease, the frequency of PB CD4(+)CD8(+)T cells had been within normal range and it gradually returned to baseline levels with the resolution of symptoms, suggesting an involvement of this population in EMM disease pathophysiology. Conclusions: This report is the first to provide a phenotypic description of lesional T cells in Mp-associated EMM. Characterizing the local immune response might help to address pathophysiological questions and warrants further systematic research

Treatment of a giant hepatic echinococcal cyst with percutaneous drainage and in vivo assessment of the protoscolicidal effect of praziquantel

Therapy choices for cystic echinococcisis (CE) are stage-specific: surgical, minimally invasive, medical or observation without intervention. PAIR (percutaneous aspiration, instillation of a scolicide, and re-aspiration) has been considered the treatment of choice for uncomplicated echinococcal liver cysts. However, PAIR carries the risk of toxic cholangitis or hypernatremia and that the cyst frequently refills with bile after withdrawing the catheter. We treated a patient with a giant CE 1 liver cyst with puncture drainage (PD) under albendazole coverage. Drainage enabled us to monitor the morphology of protoscolices under praziquantel (PZQ) co-medication. Protoscolices degenerated within 5 days of PZQ 50 mg/kg/d. The cyst cavity solidified with no evidence of reactivation or secondary spread. Percutaneous treatments can replace surgery in a significant number or cases with hepatic CE. PD allows to assess microscopically the viability of protoscolices under co-medication with PZQ-albendazole and to avoid the instillation of topical scolicides

Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion.

To clarify the physiological role of Na(+)-D-glucose cotransporter SGLT1 in small intestine and kidney, Sglt1(-/-) mice were generated and characterized phenotypically. After gavage of d-glucose, small intestinal glucose absorption across the brush-border membrane (BBM) via SGLT1 and GLUT2 were analyzed. Glucose-induced secretion of insulinotropic hormone (GIP) and glucagon-like peptide 1 (GLP-1) in wild-type and Sglt1(-/-) mice were compared. The impact of SGLT1 on renal glucose handling was investigated by micropuncture studies. It was observed that Sglt1(-/-) mice developed a glucose-galactose malabsorption syndrome but thrive normally when fed a glucose-galactose-free diet. In wild-type mice, passage of D-glucose across the intestinal BBM was predominantly mediated by SGLT1, independent the glucose load. High glucose concentrations increased the amounts of SGLT1 and GLUT2 in the BBM, and SGLT1 was required for upregulation of GLUT2. SGLT1 was located in luminal membranes of cells immunopositive for GIP and GLP-1, and Sglt1(-/-) mice exhibited reduced glucose-triggered GIP and GLP-1 levels. In the kidney, SGLT1 reabsorbed ∼3% of the filtered glucose under normoglycemic conditions. The data indicate that SGLT1 is 1) pivotal for intestinal mass absorption of d-glucose, 2) triggers the glucose-induced secretion of GIP and GLP-1, and 3) triggers the upregulation of GLUT2

Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage

Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible H2O2 at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0.1 μm. Myeloperoxidase-deficient neutrophils were predicted to accumulate large quantities of H2O2 that still effectively kill Salmonella, but most H2O2 would leak from the phagosome. Salmonella stimulation of neutrophils from normal and myeloperoxidase-deficient human donors experimentally confirmed an inverse relationship between myeloperoxidase activity and extracellular H2O2 release. Myeloperoxidase-deficient mice infected with Salmonella had elevated hydrogen peroxide tissue levels and exacerbated oxidative damage of host lipids and DNA, despite almost normal Salmonella control. These data show that myeloperoxidase has a major function in mitigating collateral tissue damage during antimicrobial oxidative bursts, by converting diffusible long-lived H2O2 into highly reactive, microbicidal and locally confined HOCl at pathogen surfaces

Carotid Artery Stenting Using a Novel Self-Expanding Braided Nickel–Titanium Stent: Feasibility and Safety Porcine Trial

We studied the deliverability and safety of a braided, self-expanding, closed-cell nickel–titanium (NiTi) stent (E-volution, Jotec GmbH, Hechingen, Germany) especially designed for the endovascular treatment of carotid artery bifurcation stenosis with special regard to in-stent stenosis and thrombosis compared with a laser-cut reference nitinol stent in a porcine model of percutaneous vascular interventions. We aimed to assess histopathologic response in minipig carotid and subclavian arteries. Eight minipigs received a total of 42 stents: 14 reference stents and 28 E-volution stents. Eleven of the E-volution stents were additionally coated with heparin. Control angiography was obtained immediately before and after vascular intervention as well as 4 weeks after the procedure. Primary endpoints were 28 days of angiographic analyses as well as histomorphometric analysis, including injury score, inflammation score, luminal diameter, vessel diameter, maximal neointimal thickness, and area of in-stent stenosis. Secondary end points were procedural success, 28-day mortality, and stent thrombosis. All stents could be delivered successfully without procedural complications, morbidity, or mortality during our observation time. As confirmed by histology, no in-stent thrombosis was observed. Compared with common carotid arteries, subclavian arteries are significantly more vulnerable to developing in-stent stenosis caused by neointima proliferation (p < 0.05). Compared with the use of 1 single stent/artery, serial application of two stents leads to a more excessive but not significantly different neointimal proliferation (p > 0.05). The E-volution stent, especially when heparin coated, is in line with the comparison to the laser-cut reference stent displaying similar results of angiographic, histologic, and histomorphometric analyses (p > 0.05). Compared with the reference laser-cut stent, the self-expanding nitinol stent (E-volution) with its advanced braiding technology is feasible and safe. In our opinion, the high radial resistive force and the advanced braided design with tight stent-strut interstices may be beneficial in terms of plaque stabilization. Further studies are necessary and warranted

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Vote Counting as Mathematical Proof

Trust in the correctness of an election outcome requires proof of the correctness of vote counting. By formalising particular voting protocols as rules, correctness of vote counting amounts to verifying that all rules have been applied correctly. A proof of the outcome of any particular election then consists of a sequence (or tree) of rule applications and provides an independently checkable certificate of the validity of the result. This reduces the need to trust, or otherwise verify, the correctness of the vote counting software once the certificate has been validated. Using a rule-based formalisation of voting protocols inside a theorem prover, we synthesise vote counting programs that are not only provably correct, but also produce independently verifiable certificates. These programs are generated from a (formal) proof that every initial set of ballots allows to decide the election winner according to a set of given rules

Reflektorelement und Verfahren zu dessen Herstellung

Es wird ein Reflektorelement (6) beschrieben, umfassend ein Kunststoffsubstrat (1), eine Silberschicht (3), eine über der Silberschicht (3) angeordnete erste Barriereschicht (4), die eine mindestens 15 nm dicke Oxidschicht ist, und eine über der ersten Barriereschicht (4) angeordnete zweite Barriereschicht (5), die ein Siloxan aufweist, wobei die Dicke der zweiten Barriereschicht (5) mindestens 250 nm und höchstens 450 nm beträgt. Weiterhin wird ein Verfahren zur Herstellung des Reflektorelements (6) beschrieben