A 3D LTCC-Based Ceramic Microfluidic System with RF Dielectric Heating of Liquids

The design, fabrication and functional evaluation of the radio-frequency dielectric heating of liquids in an LTCC-based ceramic microfluidic system are described and discussed. The device, which relies on the dielectric heating of liquids, was fabricated using a low temperature co-fired ceramic (LTCC) technology. A multilayered ceramic structure with integrated electrodes, buried channels and cavities in micro and millimetre scales was fabricated. The structure with the dimensions of 35 mm × 22 mm × 2.4 mm includes a buried cavity with a diameter of 17.3 mm and a volume of 0.3 mL. The top and bottom faces of the cavity consist of silver/palladium electrodes protected with 100 μm thick layers of LTCC. The power, used to heat a polar liquid (water) in the cavity with the volume of 0.3 mL, ranges from 5 to 40 W. This novel application of RF dielectric heating could enable the miniaturization of microfluidic systems in many applications. The working principle of such a device and its efficiency are demonstrated using water as the heated medium.     

The Immunopathogenesis of Alzheimer’s Disease Is Related to the Composition of Gut Microbiota

The microbiota–gut–brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated inflammation. Proinflammatory cytokines then trigger neuroinflammation and finally neurodegeneration. Immune-mediated oxidative stress can lead to a deficiency of vitamins and essential micronutrients. Furthermore, the wrong composition of gut microbiota might impair the intake and metabolization of nutrients. In patients with Alzheimer’s disease (AD) significant alterations of the gut microbiota have been demonstrated. Standard Western diet, infections, decreased physical activity and chronic stress impact the composition and diversity of gut microbiota. A higher abundancy of “pro-inflammatory” gut microbiota goes along with enhanced systemic inflammation and neuroinflammatory processes. Thus, AD beginning in the gut is closely related to the imbalance of gut microbiota. Modulation of gut microbiota by Mediterranean diet, probiotics and curcumin can slow down cognitive decline and alter the gut microbiome significantly. A multi-domain intervention approach addressing underlying causes of AD (inflammation, infections, metabolic alterations like insulin resistance and nutrient deficiency, stress) appears very promising to reduce or even reverse cognitive decline by exerting positive effects on the gut microbiota.     

The Nutritional Supply of Iodine and Selenium Affects Thyroid Hormone Axis Related Endpoints in Mice

Selenium and iodine are the two central trace elements for the homeostasis of thyroid hormones but additional trace elements such as iron, zinc, and copper are also involved. To compare the primary effects of inadequate intake of selenium and iodine on the thyroid gland, as well as the target organs of thyroid hormones such as liver and kidney, mice were subjected to an eight-week dietary intervention with low versus adequate selenium and iodine supply. Analysis of trace element levels in serum, liver, and kidney demonstrated a successful intervention. Markers of the selenium status were unaffected by the iodine supply. The thyroid gland was able to maintain serum thyroxine levels even under selenium-deficient conditions, despite reduced selenoprotein expression in liver and kidney, including deiodinase type 1. Thyroid hormone target genes responded to the altered selenium and iodine supply, whereas the iron, zinc, and copper homeostasis remained unaffected. There was a notable interaction between thyroid hormones and copper, which requires further clarification. Overall, the effects of an altered selenium and iodine supply were pronounced in thyroid hormone target tissues, but not in the thyroid gland.     

Polyneuropathy and dementia in old age: common inflammatory and vascular parameters

Thirty-three inpatients (22 females, 11 males, aged 79.4 ± 9.5 years) were investigated in this prospective cohort study to study the prevalence of polyneuropathy (PNP) and dementia in geriatric inpatients. Clinical and electrodiagnostic investigations, routine laboratory, including thyroid parameters, folic acid, vitamin B₁₂, homocysteine, neopterin, fibrinogen and glycosylated hemoglobin were measured in serum, the mini-mental state examination and computed tomographic scanning were performed in each patient. PNP was found clinically and electrodiagnostically in 96% of patients. Age was the most precipitating factor for PNP, and was significantly correlated to electrodiagnostic changes in the nerves investigated in both, upper and lower extremities, while clinical symptoms were confined only to the feet. Correlation was seen between homocysteine and the amplitude of the sural nerve (surAmpl) (rs = −0.406, p = 0.029) as well as the sural nerve conduction velocity (surNCV) (rs = −0.389, p = 0.037), and between neopterin and the grade of denervation (rs = 0.445, p = 0.014) in our patients. Neopterin and fibrinogen did not correlate significantly, but there was a trend to higher fibrinogen concentrations in patients with higher neopterin levels (rs = 0.344, p = 0.062). A trend of a correlation was seen between higher homocysteine concentrations and the number of changes in electrodiagnostic measurements (rs = 0.354, p = 0.055). Twenty-one of the 33 patients (64%) were demented, 9 (27%) presented clinically as mild cognitive impairment, 3 (9%) were not demented. Vascular risk factors were found in 83%: hypertension in 58%, hypercholesterinemia in 39%, cardiac disease in 36%, diabetes mellitus (DM) in 21%, peripheral arterial disease (PAD) in 9%. A significant correlation was found between homocysteine and folic acid concentrations (rs = −0.401, p = 0.028). Falls were reported in 48% of cases, indicating PNP as a risk factor in this group of patients. In conclusion, PNP was found very common with a high coincidence with dementia and a female preponderance, suggesting an influence on daily life (falls) in our subjects studied. PNP correlated significantly with markers for vascular disease as well as immune activation (homocysteine and neopterin) similar to earlier findings in patients with neurodegenerative disorders, suggesting common therapeutic options in patients with PNP and dementia.     

Metallization,Material Selection,and Bonding of Interconnections for Novel LTCC and HTCC Power Modules

Ceramic baseplates are important elements in the power modules of electric drives. This paper presents low-temperature cofired ceramic (LTCC) and high-temperature cofired ceramic (HTCC) materials for the fabrication of three-dimensional power modules. The silver-based metallization and power module assembly are presented, together with aluminum-based power wire bonding and an industrial procedure to achieve high solderability and bondability. The results of the bond tests using different metallization materials, especially cost-effective ones, are presented, together with the assembly of the power modules. The best results were achieved with Ag metallization and 380 µm Al wire and with Ag–Pd metallization and 25 µm Al wire, both on an LTCC base. The paper concludes with a dual-pulse electrical test of the power modules, which proves the quality of metallization, the type of material selected, and the correctness of the wire bonding and assembly.     

Does the aromatic L-amino acid decarboxylase contribute to thyronamine biosynthesis?

Thyronamines (TAM), recently described endogenous signaling molecules, exert metabolic and pharmacological actions partly opposing those of the thyromimetic hormone T₃. TAM biosynthesis from thyroid hormone (TH) precursors requires decarboxylation of the l-alanine side chain and several deiodination steps to convert e.g. l-thyroxine (T₄) into the most potent 3-T₁AM. Aromatic l-amino acid decarboxylase (AADC) was proposed to mediate TAM biosynthesis via decarboxylation of TH. This hypothesis was tested by incubating recombinant human AADC, which actively catalyzes dopamine production from DOPA, with several TH. Under all reaction conditions tested, AADC failed to catalyze TH decarboxylation, thus challenging the initial hypothesis. These in vitro observations are supported by detection of 3-T₁AM in plasma of patients with AADC-deficiency at levels (46 ± 18 nM, n = 4) similar to those of healthy controls. Therefore, we propose that the enzymatic decarboxylation needed to form TAM from TH is catalyzed by another unique, perhaps TH-specific, decarboxylase.