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Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Periodic revisions of the international classification of diseases (ICD) ensure that the classification reflects new practices and knowledge; however, this complicates retrospective research as diagnoses are coded in different versions. For longitudinal disease trajectory studies, a crosswalk is an essential tool and a comprehensive mapping between ICD-8 and ICD-10 has until now been lacking. In this study, we map all ICD-8 morbidity codes to ICD-10 in the expanded Danish ICD version. We mapped ICD-8 codes to ICD-10, using a many-to-one system inspired by general equivalence mappings such that each ICD-8 code maps to a single ICD-10 code. Each ICD-8 code was manually and unidirectionally mapped to a single ICD-10 code based on medical setting and context. Each match was assigned a score (1 of 4 levels) reflecting the quality of the match and, if applicable, a "flag" signalling choices made in the mapping. We provide the first complete mapping of the 8596 ICD-8 morbidity codes to ICD-10 codes. All Danish ICD-8 codes representing diseases were mapped and 5106 (59.4%) achieved the highest consistency score. Only 334 (3.9%) of the ICD-8 codes received the lowest mapping consistency score. The mapping provides a scaffold for translation of ICD-8 to ICD-10, which enable longitudinal disease studies back to and 1969 in Denmark and to 1965 internationally with further adaption. [ABSTRACT FROM AUTHOR]

It is unknown how sequential drug patterns convey information on a patient's health status and treatment guidelines rarely account for this. Drug-agnostic longitudinal analyses of prescription trajectories in a population-wide setting are needed. In this cohort study, we used 24 years of data (1.1 billion prescriptions) from the Danish prescription registry to model the risk of sequentially redeeming a drug after another. Drug pairs were used to build multistep longitudinal prescription trajectories. These were subsequently used to stratify patients and calculate survival hazard ratios between the stratified groups. The similarity between prescription histories was used to determine individuals' best treatment option. Over the course of 122 million person-years of observation, we identified 9 million common prescription trajectories and demonstrated their predictive power using hypertension as a case. Among patients treated with agents acting on the renin-angiotensin system we identified four groups: patients prescribed angiotensin converting enzyme (ACE) inhibitor without change, angiotensin receptor blockers (ARBs) without change, ACE with posterior change to ARB, and ARB posteriorly changed to ACE. In an adjusted time-to-event analysis, individuals treated with ACE compared to those treated with ARB had lower survival probability (hazard ratio, 0.73 [95% CI, 0.64–0.82]; P < 1 × 10−16). Replication in UK Biobank data showed the same trends. Prescription trajectories can provide novel insights into how individuals' drug use change over time, identify suboptimal or futile prescriptions and suggest initial treatments different from first line therapies. Observations of this kind may also be important when updating treatment guidelines. [ABSTRACT FROM AUTHOR]

Optical spectroscopy and microscopy techniques are widely used for basic studies of living systems. However, their application in clinical practice has two fundamental limitations. First, the depth of probing biological tissues with light is small and varies from tenths to several of millimeters. Secondly, it is difficult to use exogenous labels, which increase the sensitivity and specificity of pathological tissue detection, in vivo measurements on patients. This raises the question of the place of biomedical photonics among other physical diagnostic methods used in clinical practice. This article presents an review of optical methods and relatively new certified commercially available medical devices that use photonics to solve intraoperative diagnostic problems, i.e., the discrimination between pathological and healthy tissue sites in vivo and ex vivo by an endogenous optical response. This work discusses a wide range of medical fields in which researchers and engineers have been able to achieve high rates of sensitivity and specificity in solving the problem of classifying such tissues. The advantages and disadvantages of optical imaging and diagnostic methods, which determine their place in clinical practice, are discussed by the example of intraoperative diagnostics. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) is a neurodegenerative disorder that is still not fully understood. Sex modifies AD vulnerability, but the reasons for this are largely unknown. We utilize two independent electronic medical record (EMR) systems across 44,288 patients to perform deep clinical phenotyping and network analysis to gain insight into clinical characteristics and sex-specific clinical associations in AD. Embeddings and network representation of patient diagnoses demonstrate greater comorbidity interactions in AD in comparison to matched controls. Enrichment analysis identifies multiple known and new diagnostic, medication, and lab result associations across the whole cohort and in a sex-stratified analysis. With this data-driven method of phenotyping, we can represent AD complexity and generate hypotheses of clinical factors that can be followed-up for further diagnostic and predictive analyses, mechanistic understanding, or drug repurposing and therapeutic approaches. Sex modifies Alzheimer's Disease vulnerability, but the reasons for this are largely unknown. Here, the authors utilize two independent electronic medical record systems to perform deep clinical phenotyping and network analysis to gain insight into clinical characteristics and sex-specific clinical associations. [ABSTRACT FROM AUTHOR]

It is unknown how sequential drug patterns convey information on a patient's health status and treatment guidelines rarely account for this. Drug-agnostic longitudinal analyses of prescription trajectories in a population-wide setting are needed. In this cohort study, we used 24 years of data (1.1 billion prescriptions) from the Danish prescription registry to model the risk of sequentially redeeming a drug after another. Drug pairs were used to build multistep longitudinal prescription trajectories. These were subsequently used to stratify patients and calculate survival hazard ratios between the stratified groups. The similarity between prescription histories was used to determine individuals' best treatment option. Over the course of 122 million person-years of observation, we identified 9 million common prescription trajectories and demonstrated their predictive power using hypertension as a case. Among patients treated with agents acting on the renin-angiotensin system we identified four groups: patients prescribed angiotensin converting enzyme (ACE) inhibitor without change, angiotensin receptor blockers (ARBs) without change, ACE with posterior change to ARB, and ARB posteriorly changed to ACE. In an adjusted time-to-event analysis, individuals treated with ACE compared to those treated with ARB had lower survival probability (hazard ratio, 0.73 [95% CI, 0.64–0.82]; P < 1 × 10−16). Replication in UK Biobank data showed the same trends. Prescription trajectories can provide novel insights into how individuals' drug use change over time, identify suboptimal or futile prescriptions and suggest initial treatments different from first line therapies. Observations of this kind may also be important when updating treatment guidelines. [ABSTRACT FROM AUTHOR]

Concentrated solar radiation (CSR)-assisted synthesis of pyranopyrazole derivatives under solvent and catalyst-free condition has been reported in the present protocol. One-pot multicomponent synthesis from aromatic/heteroaldehyde, ethyl acetoacetate, malononitrile, and hydrazine hydrate leads to the final desired compounds in a good yield. This operationally simple methodology has several advantages such as green and clean reaction profile, simple workup and purification procedures, extremely short reaction time, atom efficiency, and being economical. The current energy-efficient method saves almost 98% of energy as compared to the conventional method. [ABSTRACT FROM AUTHOR]

The importance of quantifying the distribution and determinants of multimorbidity has prompted novel data-driven classifications of disease. Applications have included improved statistical power and refined prognoses for a range of respiratory, infectious, autoimmune, and neurological diseases, with studies using molecular information, age of disease incidence, and sequences of disease onset ("disease trajectories") to classify disease clusters. Here we consider whether easily measured risk factors such as height and BMI can effectively characterise diseases in UK Biobank data, combining established statistical methods in new but rigorous ways to provide clinically relevant comparisons and clusters of disease. Over 400 common diseases were selected for analysis using clinical and epidemiological criteria, and conventional proportional hazards models were used to estimate associations with 12 established risk factors. Several diseases had strongly sex-dependent associations of disease risk with BMI. Importantly, a large proportion of diseases affecting both sexes could be identified by their risk factors, and equivalent diseases tended to cluster adjacently. These included 10 diseases presently classified as "Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified". Many clusters are associated with a shared, known pathogenesis, others suggest likely but presently unconfirmed causes. The specificity of associations and shared pathogenesis of many clustered diseases provide a new perspective on the interactions between biological pathways, risk factors, and patterns of disease such as multimorbidity. [ABSTRACT FROM AUTHOR]

Atmospheric pressure plasma jets generated using noble gases have been the focus of intense investigation for over 2 decades due to their unique physicochemical properties and their suitability for treating living tissues to elicit a controlled biological response. Such devices enable the generation of a non-equilibrium plasma to be spatially separated from its downstream point of application, simultaneously providing inherent safety, stability and reactivity. Underpinning key plasma mediated biological applications are the reactive oxygen and nitrogen species (RONS) created when molecular gases interact with the noble gas plasma, yielding a complex yet highly reactive chemical mixture. The interplay between the plasma physics, fluid dynamics and plasma chemistry ultimately dictates the chemical composition of the RONS arriving at a biological target. This contribution reviews recent developments in understanding of the interplay between the flowing plasma, the quiescent background and a biological target to promote the development of future plasma medical therapies. [ABSTRACT FROM AUTHOR]

Data platforms represent a new paradigm for carrying out health research. In the platform model, datasets are pooled for remote access and analysis, so novel insights for developing better stratified and/or personalised medicine approaches can be derived from their integration. If the integration of diverse datasets enables development of more accurate risk indicators, prognostic factors, or better treatments and interventions, this obviates the need for the sharing and reuse of data; and a platform-based approach is an appropriate model for facilitating this. Platform-based approaches thus require new thinking about consent. Here we defend an approach to meeting this challenge within the data platform model, grounded in: the notion of ‘reasonable expectations’ for the reuse of data; Waldron’s account of ‘integrity’ as a heuristic for managing disagreement about the ethical permissibility of the approach; and the element of the social contract that emphasises the importance of public engagement in embedding new norms of research consistent with changing technological realities. While a social contract approach may sound appealing, however, it is incoherent in the context at hand. We defend a way forward guided by that part of the social contract which requires public approval for the proposal and argue that we have moral reasons to endorse a wider presumption of data reuse. However, we show that the relationship in question is not recognisably contractual and that the social contract approach is therefore misleading in this context. We conclude stating four requirements on which the legitimacy of our proposal rests. [ABSTRACT FROM AUTHOR]

Copyright of Der Pneumologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although the dichlorofluorescein (DCF) assay is widely used to detect the production of UVA-induced ROS, the photostability and phototoxicity of the probe after UVA irradiation remains controversial and the experimental conditions often vary across studies, making it difficult to compare results from different studies. This study aimed to evaluate the suitability of the DCF assay for detection of UVA-induced ROS in human cells after UVA irradiation. Human primary fibroblasts (HPF) and HaCaT cells were loaded with 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) (2, 10, and 50 μM) for 10 and 30 min, before and after exposure to UVA radiation (5–50 J cm−2). Fluorescence was recorded immediately or 30 min after irradiation using three different techniques: microplate reading, flow cytometry, and confocal scanning microscopy. Cell viability was assessed by flow cytometry before and after UVA exposure. A UVA-dose-dependent increase in ROS was observed at 5–50 μM DCFDA, and the magnitude of the fluorescent signal was affected by RPMI medium, as well as DCFDA loading concentration and incubation period. However, higher concentrations of DCFDA compromised the viability of both HaCaT and HPF cells after UVA irradiation. The most sensitive and reliable combination for the ROS assay was pre-incubation with 10 μM DCFDA for 30 min in PBS. Reading the fluorescence 30 min after UVA irradiation diminished the emission signal, as did the DCFDA post-incubation. In conclusion, this single-point DCF assay allowed reproducible and sensitive UVA-induced ROS detection in HaCaT and HPF cells without compromising the cell viability or morphology. [ABSTRACT FROM AUTHOR]

The possibility to use oral intake of fluorescent dyes approved on humans for intravital fluorescence in vivo imaging is attractive due to its simplicity and non-invasive character. Here we investigate the potential of solid lipid curcumin particles (SLCP) for imaging of capillary permeability using fluorescence video capillaroscopy. Curcumin fluorescence corresponding to 0.7 μg/mL concentration was observed from blood plasma after oral consumption of 2 g of SLCP. However, this signal was ~15% higher than that of blood plasma intrinsic fluorescence, which was itself at least 10-fold lower than the background signal from pericapillary tissue. By comparing the optical properties and concentration to the case of intravenous injection of sodium fluorescein, we analyzed which parameters of the experiment should be optimized for using oral consumption of fluorescing compounds in intravital in vivo capillaroscopy measurements. [ABSTRACT FROM AUTHOR]

This short review describes recent progress in using optical clearing (OC) technique in skin studies. Optical clear-ing is an efficient tool for enhancing the probing depth and data quality in multiphoton microscopy and Raman spec-troscopy. Here, we discuss the main mechanisms of OC, its safety, advantages, and limitations. The data on the OC effect on the skin water content are presented. It was demonstrated that 70% glycerol and 100% OmnipaqueTM 300 reduce the water content in the skin. Both OC agents (OCAs) significantly affect the strongly bound and weakly bound water. However, OmnipaqueTM 300 causes considerably less skin dehydration than glycerol. In addition, the results of examination of the OC effect on autofluorescence in two-photon excitation and background fluorescence in Raman scattering at different skin depths are presented. It is shown that OmnipaqueTM 300 is a promising OCA due to its ability to reduce background fluo-rescence in the upper skin layers. The possibility of multimodal imaging combining optical methods and OC technique is discussed. [ABSTRACT FROM AUTHOR]

Carotenoids, found in many fruits and vegetables, are antioxidants that protect human skin from UV radiation. In humans, fruit and vegetable intake increases carotenoid contents in skin, which are conventionally assessed by invasive blood tests. In this study, 47 healthy Korean subjects (volunteers) consumed fruit juice containing tomato, apple, strawberry, or grape three times per week for 6 weeks. Skin antioxidant levels were measured by non-invasive resonance Raman spectroscopy. The correlation between skin carotenoid (SC) score with demographic data (age, height, weight) and juice supplementation and changes in SC scores among groups were analyzed. Variations in skin antioxidant levels increased with juice supplementation (p < 0.05). Fruit juice intake was significantly correlated with SC score, indicating increased skin antioxidant levels. Grape and tomato increased skin antioxidant levels and showed higher antioxidant activity than other fruits. Fruit juices containing high levels of carotenoids and antioxidants may provide modest benefits to human health. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis pneumonia (PCP) is an opportunistic and potentially life-threatening infection of immunocompromised individuals. A combination of trimethoprim-sulfamethoxazole is widely used for prophylaxis and treatment of PCP. Polymorphisms in the drug targets, the dihydropteroate synthase (DHPS) or the dihydrofolate reductase (DHFR) are presumably a reason for treatment failure. Methods: We retrospectively examined the prevalence of DHPS and DHFR mutations in Pneumocystis jirovecii isolates obtained from HIV-infected and non-HIV-infected PCP patients. DHFR and DHPS genes were amplified using semi-nested PCR followed by sequencing. Obtained data were correlated with clinical findings. Results: Sequencing of the DHPS gene was achieved in 81 out of 128 isolates (63%), the DHFR-gene was successfully sequenced in 96 isolates (75%). The vast majority of DHFR and DHPS sequences were either wild-type or showed synonymous single nucleotide polymorphisms. Only one sample contained a double mutation at DHPS codon 55 and codon 57 which was associated with treatment failure in some studies. No linkage of treatment failure to a DHFR or DHPS genotype was observed. In our cohort, 35 of 95 Patients (37%) were HIV-positive and 60 (63%) were HIV-negative. The overall mortality rate was 24% with a much higher rate among non-HIV patients. Conclusion: DHPS and DHFR mutations exist but are infrequent in our cohort. The contribution of gene polymorphisms to treatment failure needs further research. In immunocompromised HIV-negative patients PCP is associated with high mortality rates. Prophylactic treatment is warranted in this patient subset. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Many sunscreens incorporate agents that are said to protect against infrared (IR) damage in the skin but we lack any real data on their benefit in the context of normal human behaviour in the sun. The object of this study was to examine typical IR exposure levels to the sun and industrial sources in order to decide whether there is a need for sunscreens to contain agents that protect against IR radiation, specifically the IR-A waveband. We reviewed claims currently made by products offering protection against IR-A and studies on the biological and clinical effects attributed to IR-A, and compared IR-A exposure levels from these studies with those typically received from the sun and from industrial sources. We found that annual levels of IR-A exposure resulting from typical behaviour in the sun are commensurate with those experienced occupationally by workers exposed to industrial sources of IR, such as steel and glass furnaces. Yet these workers appear to suffer little in the way of chronic skin damage. We conclude that there is not compelling evidence to demonstrate that observable, deleterious cutaneous effects are occurring at doses of solar IR radiation corresponding to those experienced by populations in their normal environments and for this reason we believe it is premature to incorporate IR protection into topical sunscreens and to make claims related to ageing of the skin that consumers may expect to see. [ABSTRACT FROM AUTHOR]

In contrast to malaria, multiple sclerosis (MS) is infrequently found in Black Africans. We describe a 29 year old Nigerian female who developed an MS-like condition with symptoms similar to relapsing-remitting MS following malaria infection, leading to a diagnosis of MS. However, absence of hyperintense lesions in the brain and spinal cord presented a conundrum since not all the diagnostic criteria for MS were met. Pathology supported genetic testing (PSGT) was applied to combine family and personal medical history, lifestyle factors, and biochemical test results for interpretation of genetic findings. This approach provides a means of identifying risk factors for different subtypes of demyelinating disease. The patient was subsequently treated according to an individualised intervention program including nutritional supplementation as well as a change in diet and lifestyle. Deficiencies of vitamin B12, iron and vitamin D were addressed. Genetic analysis revealed absence of the HLA DRB1*1501 allele, considered to be the most prominent genetic risk factor for MS. Extended mutation analysis identified variations in three genes in the folate-vitamin B12 metabolic pathway, which could have increased the patient's sensitivity to the antifolate drugs used to treat the malaria. A glutathione-S-transferase GSTM1 null allele, previously associated with neurological complications of malaria, was also detected. Furthermore, a heterozygous variation in the iron-related transmembrane protease serine 6 ( TMPRSS6) gene, rs855791 was found, which could have impacted the patient's iron status following two successive blood donations and exposure to malaria preceding the MS diagnosis. PSGT identifies relevant risk factors for demyelinating disorders resembling MS and uses the data for individualised treatment programs, and to systematically build a database that can provide evidence in large patient cohorts. Follow-up investigations may be suggested, such as whole exome sequencing in selected cases, to ensure that remyelination and restoration of function are achieved. [ABSTRACT FROM AUTHOR]

The present study was undertaken to detect Pneumocystis jirovecii infection among HIV-positive patients presenting with symptoms of lower respiratory tract infection and analyze the associated dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) mutations. P. jirovecii infection was detected in 12.6 % cases. We did not find DHPS gene mutations at the commonest positions of codon 55 and 57; however, mutation at codon 171 was detected in two cases. No mutations in DHFR gene were detected. The results indicate low prevalence of DHPS and DHFR mutations in Indian P. jirovecii isolates, suggesting that the selective pressure of sulfa drugs on the local strains has probably not reached the levels found in developed nations. [ABSTRACT FROM AUTHOR]

Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) are demyelinating disorders affecting the central nervous system. An autoimmune aetiology has been proposed for both. ADEM principally affects adolescents following acute infection by a variety of pathogens and has also been reported to occur following vaccination. ADEM typically resolves following medical treatment, whereas MS follows a more relapsing and remitting course. The pathogenesis of MS remains unclear, but it is thought that a combination of infectious and non-infectious environmental factors and host genetics act synergistically to cause disease. A variety of viruses, including Epstein Barr virus, cytomegalovirus, herpes simplex virus and varicella zoster virus, have been implicated as possible infectious triggers. The similar clinical and pathological presentation of ADEM and MS presents a diagnostic challenge for distinguishing ADEM from a first episode of MS. Some cases of ADEM progress to MS for reasons that are not currently clear. This review examines the evidence for infectious agents as triggers for ADEM progressing to MS and suggests potential methods that may facilitate identification of infectious agents that may be responsible for the pathogenesis of ADEM to MS. [ABSTRACT FROM AUTHOR]

Near infrared spectroscopy (NIRS) may be utilized in conjunction with a vascular occlusion test to quantify a tissue bed's ability to re-oxygenate by measuring continuous tissue oxygen saturation recovery rate. We hypothesize that NIRS recovery slope will be associated with expression of endothelial biomarkers, thus, making it a feasible bedside surrogate for assessing endothelial activation/dysfunction in patients with sepsis. A secondary analysis of a prospective, multicenter, observational study was done on a convenience sample of adult patients at four university emergency departments consisting of patients with septic shock, sepsis without shock and patients without infection. At enrollment we measured the NIRS-derived measurements and collected plasma to assay biomarkers of endothelial activation. 186 patients were enrolled in the study. The mean age was 63 (±16) years with 60 % male gender. Univariate analysis assessing the linear relationship between the recovery slope with endothelial biomarkers, found a weak but statistical significant association between NIRS recovery slope and soluble fms-like tyrosine kinase-1 (sFLT-1) and tPAI-1 ( r = −0.08, p < 0.0001 and r = −0.06, p = 0.002). When adjusting for diabetes, age and sequential organ failure assessment score at enrollment, only sFLT-1 persisted having a statistically significant association ( r = −0.04, p = 0.01). We found a weak, but statistically significant relationship between NIRS-derived measurements and biomarkers of endothelial activation/dysfunction in patients with sepsis. This study fails to support the use of NIRS-derived measurements as a clinical or research tool to identify patients with endothelial cell activation/dysfunction and informs researchers that this is not a robust option for identifying this lesion at the bedside. [ABSTRACT FROM AUTHOR]

Anaplasma phagocytophilum has been first isolated from the blood of two Czech patients simultaneously with a cultivation of Borrelia burgdorferi sensu lato from their erythema migrans lesions. Cultivation of different Borrelia spp. from 12 erythema migrans biopsies, from 2 blood, one liquor and one placenta sample in BSK-H medium was successful. Adapted conventional methods targeting 16S rRNA and OspA genes for real-time polymerase chain reaction (PCR) and partial sequencing of these genes together with microscopical examinations of the blood smears provided a direct detection of the B. afzelii, B. burgdorferi, B. garinii, B. valaisiana and B. bissettii in the skin, B. garinii in the blood, placenta and liquor in 24 (36.3 %) patients, and A. phagocytophilum in 10 (15 %) patients with erythema migrans. Positive indirect IgM immunofluorescence against Anaplasma sp. was obtained in 7 cases, specific IgG antibodies were detected in 12 patients. Three women suffering from erythema migrans in the first trimester had positive PCR for Anaplasma and/or for Borrelia in the blood and two of them, later, in the placenta. Interpretation of laboratory data can bring important contribution to establishing the role of Anaplasma sp. in erythema migrans and forming the principle of precaution with laboratory diagnosis during pregnancy which always should be reflected in the resistance of Anaplasma sp. toward penicillins. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The yellow fever vaccine plays an essential role in protecting humans from yellow fever, and millions of doses are administered each year. The attenuated live-virus vaccine has long been considered to be among the safest and most effective vaccines. Newly recognized rare, but sometimes fatal, adverse events associated with the vaccine have prompted scrutiny of the traditional recommendations for use of the vaccine and have raised questions about their pathogenesis. This paper describes the adverse events associated with the vaccine, reviews postulated reasons for the recent recognition of these events, discusses key research questions that need to be addressed in trying to understand their origin and risk factors, and reviews current indications for the use of the vaccine. Knowledge of the epidemiology of yellow fever is necessary to make informed recommendations. Current surveillance is inadequate to provide a precise exposure risk for most travelers. [ABSTRACT FROM AUTHOR]

To investigate the influence of pre-existing antibodies against tick-borne encephalitis (TBE) or yellow fever (YF) viruses on dengue virus antibody test results, we examined sera from vaccinees and from individuals with previous TBE virus infection. Distinct IgG antibody cross-reactivity was found in about 15.1% in the YF-vaccinated group and in about 9.5% in the TBE-vaccinated group. Altogether 15 out of a total of 80 samples tested (18.8%) had detectable dengue virus IgG antibody titres. The serum samples from patients with acute TBE virus infection not only had the highest anti-TBE virus antibodies but were also highly cross-reactive against dengue virus antigens. The high cross-reactivity rate of YF and TBE antibody-positive sera in dengue virus antibody assays should be taken into account in the interpretation of laboratory tests for the diagnosis of flavivirus infections and when undertaking seroepidemiological surveys. [ABSTRACT FROM AUTHOR]

A 4-y-old girl was admitted with fever and altered sensorium. Peripheral blood smear and quantified buffy coat test showed Plasmodium falciparum infection. She received antimalarial therapy and got discharged on seventh day without any neurological deficit. Seven days later she was readmitted with fever and disorientation. Neurological examination revealed coma and decerebration. The deep tendon reflexes were exaggerated and babiniski response was positive in the right lower limb. MRI of brain revealed multifocal asymmetrical T2W/FLAIR hyperintensities in cerebral hemispheres, sub cortical white matter and midbrain. There was minimal patchy enhancement on contrast study. Any feature of grey matter involvement was not observed. The child improved remarkably after the treatment with methyl prednisolone. A follow up MRI after one year showed a complete resolution of demyelinating lesions. Diagnosis of acute disseminated encephalomyelitis (ADEM) as a complication of falciparum malaria was made based on sudden onset of neurological events, MRI findings and prompt response to corticosteroid therapy. [ABSTRACT FROM AUTHOR]

Three Austrian travelers (a 37-year-old woman, a 47-year-old woman and a 47-year-old man) presented with fever, dyspnea, thoracodynia, cephalea, arthralgia and fatigue 4 weeks after visiting a bat cave in Mexico. Computed tomography of the lungs showed bilateral nodular infiltrates in all three patients and enlarged mediastinal lymphnodes in two patients. In all patients, specific IgM antibodies against Histoplasma capsulatum could be detected. After treatment with itraconazole 200 mg qd orally for 2 months, the patients had no further complaints and the pulmonary infiltrates had resolved. [ABSTRACT FROM AUTHOR]

We present the Danish Disease Trajectory Browser (DTB), a tool for exploring almost 25 years of data from the Danish National Patient Register. In the dataset comprising 7.2 million patients and 122 million admissions, users can identify diagnosis pairs with statistically significant directionality and combine them to linear disease trajectories. Users can search for one or more disease codes (ICD-10 classification) and explore disease progression patterns via an array of functionalities. For example, a set of linear trajectories can be merged into a disease trajectory network displaying the entire multimorbidity spectrum of a disease in a single connected graph. Using data from the Danish Register for Causes of Death mortality is also included. The tool is disease-agnostic across both rare and common diseases and is showcased by exploring multimorbidity in Down syndrome (ICD-10 code Q90) and hypertension (ICD-10 code I10). Finally, we show how search results can be customized and exported from the browser in a format of choice (i.e. JSON, PNG, JPEG and CSV). The Danish health system has been collecting health-related data on the entire Danish population for years. Here the authors present the Danish Disease Trajectory Browser (DTB), which allows users to explore population-wide disease progression patterns from data collected between 1994 and 2018. [ABSTRACT FROM AUTHOR]

Little is known about enduring memory B cell (MBC) responses to Zika virus (ZIKV) and their relationship with circulating antibodies. Here we comprehensively assess MBC frequency and specificity alongside serum binding and neutralizing antibody responses to ZIKV ~2 weeks and ~8 months postinfection in 31 pediatric subjects with 0, 1 or >1 prior infections with the related dengue virus (DENV). ZIKV infection elicits a robust type-specific MBC response, and the majority of late convalescent anti-ZIKV serum neutralizing activity is attributable to ZIKV-specific antibodies. The number of prior DENV infections does not influence type-specific or cross-reactive MBC responses, although ZIKV has the highest cross-reactivity with DENV3. DENV cross-reactive MBCs expanded by ZIKV infection decline in number and proportion by late convalescence. Finally, ZIKV induces greater cross-reactivity in the MBC pool than in serum antibodies. Our data suggest immunity to DENV only modestly shapes breadth and magnitude of enduring ZIKV antibody responses. Here, Andrade et al. assess the memory B cell (MBC) and antibody response to Zika virus (ZIKV) in individuals with and without prior dengue virus (DENV) infection and find that ZIKV infection elicits a robust and specific MBC response that is only modestly affected by the number of prior DENV infections. [ABSTRACT FROM AUTHOR]

There is insufficient evidence to support screening of various tick-borne diseases (TBD) related microbes alongside Borrelia in patients suffering from TBD. To evaluate the involvement of multiple microbial immune responses in patients experiencing TBD we utilized enzyme-linked immunosorbent assay. Four hundred and thirty-two human serum samples organized into seven categories followed Centers for Disease Control and Prevention two-tier Lyme disease (LD) diagnosis guidelines and Infectious Disease Society of America guidelines for post-treatment Lyme disease syndrome. All patient categories were tested for their immunoglobulin M (IgM) and G (IgG) responses against 20 microbes associated with TBD. Our findings recognize that microbial infections in patients suffering from TBDs do not follow the one microbe, one disease Germ Theory as 65% of the TBD patients produce immune responses to various microbes. We have established a causal association between TBD patients and TBD associated co-infections and essential opportunistic microbes following Bradford Hill’s criteria. This study indicated an 85% probability that a randomly selected TBD patient will respond to Borrelia and other related TBD microbes rather than to Borrelia alone. A paradigm shift is required in current healthcare policies to diagnose TBD so that patients can get tested and treated even for opportunistic infections. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about yellow fever vaccine viremia following bone marrow (BM) suppression in acute myeloid leukemia (AML).

Acute demyelinating encephalomyelitis usually follows viral infections and its occurrence following malarial infection is very uncommon. We report a 12-year-old girl who presented with encephalopathy and generalized convulsions following complete recovery from the Plasmodium falciparum infection. Diagnosis of ADEM was made on the basis of brain MRI findings. [ABSTRACT FROM AUTHOR]