Management of the early stage of Alzheimer's disease: a systematic review of literature over the past 10 years.

BACKGROUND: Alzheimer's disease is the most widespread senile dementia in the world and diagnoses are on the rise due to the aging of the world's population and this is causing a significant increase in health spending on the care of the disease. Current studies highlight the need for rapid diagnosis in order to prevent the therapeutic approach from being ineffective, and a comprehensive management of the disease, both with pharmacological and integrative therapies (safety of the environment, music therapy, diet, physical activity, recreational activities, etc.). Regarding the care provided by caregivers, the need to educate these figures is fundamental, to support them economically and psycho-socially (especially during the most difficult stages of the disease) and to provide them with technical skills to effectively and safely address the patient's care. OBJECTIVES: Aim of this study was to investigate the current evidence from scientific literature about the early stage of Alzheimer's disease in order to educate and support caregivers with specific technical and practical skills. MATERIAL AND METHODS: A systematic review of the scientific literature of the last 10 years, has been conducted in September 2019 through Medline (PubMed), Scopus and Cinahl databases, in accordance with the criteria of PRISMA Statement guideline (Preferred Reporting Items for Systematic reviews and Meta-Analyses). The included studies were related to Alzheimer's disease and patients' management. RESULTS: Thirty-six articles met the inclusion criteria but only for 26 of these it was possible to retrieve and access the full text. CONCLUSIONS: The evidences from this study provide information on how to effectively address Alzheimer's disease. The studies address different aspects of the disease, with different methodologies, thus providing heterogeneous evidence. Future studies with reproducible methodologies should be undertaken in order to achieve robustness in results.

Dexamethasone and prednisolone treatment in beef cattle: influence on glycogen deposition and gene expression in the liver.

The illegal administration of glucocorticoids in livestock is problematic and identification of pathways in which these hormones are involved is critically important, and new direct or indirect biomarkers should be identified. In this work, glucocorticoid transcriptional effects on some genes involved in the glucose metabolism were studied in the bovine liver. This study was conducted on adult Charolais male cattle treated with long-term low dose dexamethasone or prednisolone. Gene expression analysis was conducted in the liver by qPCR, and the geNorm algorithm was applied to select optimal reference genes. In line with the literature, a significant overexpression of genes involved in the gluconeogenic pathway and glycogen synthesis was detected in the liver of dexamethasone-treated animals, but histological and biochemical examination showed hepatocyte glycogen depletion particularly in dexamethasone-treated animals. It possible to hypothesize that glucocorticoids or adrenal insufficiency due to glucocorticoids withdrawal inhibit the enzymatic activity of glycogen synthase and/or induce glycogen autophagy in bovine liver. In fact, markers of glycophagy as starch-binding domain-containing protein 1 and γ-aminobutyric acid receptor-associated protein-like 1 mRNAs were upregulated in the liver by glucocorticoids treatment. Furthermore, glycogen synthase kinase-3 beta gene was significantly overexpressed in dexamethasone-treated animals, and this protein is also implicated in liver autophagy modulation and glycogen synthesis inhibition. These results showed that glucocorticoids likley have dual roles in hepatic glycogen metabolism of cattle, and investigation of these pathways could help find treatment biomarkers.

Energetic material response to ultrafast indirect laser heating.

The initial evolution of thermal energy transfer into a solid explosive is studied using an indirect femtosecond laser heating technique on a picosecond timescale in order to elucidate the role of temperature in the shock-induced initiation of explosives. The indirect laser heating method is presented; time-resolved visible transient absorption (TA) spectroscopy was used to monitor the energetic material response following heat transfer from the laser-heated gold (Au) layer to the sample. Reported here are visible TA data in the spectral region from 500 to 750 nm for indirect laser-heated thin films of cyclotrimethylene trinitramine (RDX), oxidized polyethylene (OPE), and RDX with 1%, 2.5%, 5%, or 10% OPE prior to decomposition. TA was observed for RDX and RDX with OPE; however, no TA was observed for pure OPE. Compared to pure RDX, the TA intensity of RDX with OPE decreases as the OPE content increases and the time required to observe the TA signal from RDX increases. Our results suggest that the thermal energy produced by a femtosecond laser pulse with an energy of 15 mJ cm-2 is sufficient to induce changes in the electronic structure of RDX, resulting in promotion of the RDX molecules into an excited state. We also determined that the heat transfer rate in RDX depends on its homogeneity and degree of purity.

Thermal poling of silica optical fibers using liquid electrodes.

Thermal poling is a well-known technique for inducing second-order nonlinearities in centrosymmetric silica optical fibers. However, some 25 years since its discovery, there still remain a number of issues that prevent the realization of very long length, highly efficient all-fiber nonlinear device applications that include frequency conversion or sources of polarization-entangled photon pairs. In this Letter, we report a thermal poling method that utilizes a novel range of liquid metal and aqueous electrodes embedded into the optical fibers. We demonstrate that it is possible to pole samples that are potentially meters in length, characterized by very low losses for efficient second-harmonic generation processes. The maximum estimated effective value of χ(2) (0.12 pm/V) obtained using mercury electrodes is the highest reported in periodically poled silica fibers.

A rigorous detection of interstellar CH3NCO: An important missing species in astrochemical networks.

The recent analysis of the composition of the frozen surface of comet 67P/Churyumov-Gerasimenko has revealed a significant number of complex organic molecules. Methyl isocyanate (CH3NCO) is one of the more abundant species detected on the comet surface. In this work we report extensive characterization of its rotational spectrum resulting in a list of 1269 confidently assigned laboratory lines and its detection in space towards the Orion clouds where 399 lines of the molecule have been unambiguously identified. We find that the limited mm-wave laboratory data reported prior to our work require some revision. The abundance of CH3NCO in Orion is only a factor of ten below those of HNCO and CH3CN. Unlike the molecular abundances in the coma of comets, which correlate with those of warm molecular clouds, molecular abundances in the gas phase in Orion are only weakly correlated with those measured on the comet surface. We also compare our abundances with those derived recently for this molecule towards Sgr B2 (Halfen et al. 2015). A more accurate abundance of CH3NCO is provided for this cloud based on our extensive laboratory work.

Optical fiber poling by induction: analysis by 2D numerical modeling.

Since their first demonstration some 25 years ago, thermally poled silica fibers have been used to realize device functions such as electro-optic modulation, switching, polarization-entangled photons, and optical frequency conversion with a number of advantages over bulk free-space components. We have recently developed an innovative induction poling technique that could allow for the development of complex microstructured fiber geometries for highly efficient χ(2)-based device applications. To systematically implement these more advanced poled fiber designs, we report here the development of comprehensive numerical models of the induction poling mechanism itself via two-dimensional (2D) simulations of ion migration and space-charge region formation using finite element analysis.

Open sphincter-preserving surgery of extraperitoneal rectal cancer without primary stoma and Fast Track Protocol.

AIM: Fast track protocol (FTP) showed to improve perioperative care. The study aims to evaluate the impact of the FTP in the open extraperitoneal rectal cancer (ERC) surgical treatment without a primary derivative stoma (DS) and the QoL in patients with or without a secondary DS. PATIENTS AND METHODS: 50 patients affected by ERC were enrolled and operated on with open low anterior resection without a primary DS. They were randomized in two groups: one was treated perioperativelly in the traditional way (group T), the other using a modif ed FTP (group FT). A QoL questionnaire was administered prior to discharge and at 1-month follow-up. RESULTS: Five courses (10%) were complicated by anastomotic leakage: 3 (12%) in the FT group (2 minor and 1 maior) and 2 (8%) in the T group (1 minor and 1 maior) (p=n.s.). All the maiors and one minor were treated with a DS. Patients of the group FTP were considered dischargeable earlier that those of group T (p<0.05). Patients with DS had a significantly lower QoL score (p<0.0001). CONCLUSION: FTP with minor modifications is feasible and safe in the ERC open surgery without using a DS. Better results were obtained without increasing complication rate. A secondary DS impacts detrimentally on QoL.

A comparison of the outcome using Ligasure™ small jaw and clamp-and-tie technique in thyroidectomy: a randomized single center study.

PURPOSE: Hypoparathyroidism and paralysis of the recurrent laryngeal nerve (RLN) still remain the most frequent specific complications of thyroid surgery. This study evaluates the effects of employment of a recently introduced device (LigaSure™ Small Jaw, LSJ), compared to the traditional clamp-and-tie (CT) technique, on the short- and long-term outcome of the patients who underwent thyroidectomy. METHODS: This prospective, randomized study included 190 patients enrolled from October 2011 to July 2013. The numbers of patients in the LSJ group and the CT group were both 95. We studied the following: operative times, intraoperative and postoperative blood losses, intact parathormone (iPTH) and calcium serum levels, and the incidence of RLN paralysis. RESULTS: The two cohorts were homogeneous for age, sex, surgical indication, BMI, ASA score, and estimated thyroid volume. Operation time has been 73.90 ± 23.35 min in group CT and 60.20 ± 22.36 min in group LSJ (p = 0.002). Intraoperative blood losses have been 47 ± 18 ml in group CT and 38 ± 14 in group LSJ (p = 0.002), while postoperative blood losses have been 45 ± 21 ml in group CT and 40 ± 20 in group LSJ (p = 0.105). The mean calcium blood level in group CT has been 8.12, 7.79, and 7.92 mg/dl in the first, second, and third postoperative days, respectively, as well as 8.26, 7.97, and 8.22 mg/dl for group LSJ (p > 0.05). Basal and post-thyroidectomy iPTH levels have been 46.49 and 23.64 pg/ml in group CT (Δ = 49.15 %), as well as 51.06 and 27.73 (Δ = 45.69 %) in group LSJ (p > 0.05). Permanent RLN paralysis was 1.05 % in LSJ group and 0 % in CT group. CONCLUSION: The employment of LSJ reduces in a statistically significant way both operative times and intraoperative blood losses. No significant differences were found as far as postoperative RLN paralysis and hypoparathyroidism.

Optical fiber poling by induction.

Conventional thermal poling methods require direct physical contact to internal fiber electrodes. Here, we report an indirect electrostatic induction technique using electrically floating wires inside the fiber combined with external electric fields that can allow for facile poling of complex microstructured fibers (MOFs) of arbitrarily long lengths. In combination with our unique ability to use liquid gallium electrodes, inducing second-order nonlinearities inside otherwise difficult to access multi-core or multi-hole MOFs now becomes entirely feasible and practical. The formation of a permanent second-order nonlinearity is unequivocally demonstrated by realizing quasi-phase-matched frequency doublers using periodic UV erasure methods in the induction-poled fibers. The second-order susceptibility created inside the fiber is driven by the potential difference established between the floating electrodes, which we calculate via numerical simulations.

Decline of the Mediterranean diet at a time of economic crisis. Results from the Moli-sani study.

BACKGROUND AND AIMS: Adherence to Mediterranean diet (MD) is reportedly declining in the last decades. We aimed to investigate the adherence to MD over the period 2005-2010 and exploring the possible role of the global economic crisis in accounting for the changing in the dietary habits in Italy. METHODS AND RESULTS: Cross-sectional analysis in a population-based cohort study which randomly recruited 21,001 southern Italian citizens enrolled within the Moli-sani study. Food intake was determined by the Italian EPIC food frequency questionnaire. Adherence to MD was appraised by the Italian Mediterranean Index (IMI). A wealth score was derived to evaluate the economic position and used together with other socioeconomic indicators. Highest prevalence of adherence to MD was observed during the years 2005-2006 (31.3%) while the prevalence dramatically fell down in the years 2007-2010 (18.3%; P<0.0001). The decrease was stronger in the elderly, less affluent groups, and among those living in urban areas. Accordingly, we observed that in 2007-2010 socioeconomic indicators were strongly associated with higher adherence to MD, whereas no association was detected in the years before the economic crisis began; both wealth score and education were major determinants of high adherence to MD with 31% (95%CI: 18-46%) higher adherence to this pattern within the wealthier group compared to the less affluent category. CONCLUSION: Adherence to MD has considerably decreased over the last few years. In 2007-2010 socioeconomic indicators have become major determinants of adherence to MD, a fact likely linked to the economic downturn.

Effect of gender and geographic location on the expression of primary hyperparathyroidism.

BACKGROUND: The effect of gender on the expression of primary hyperparathyroidism (PHPT) is not well characterized. AIM: We therefore evaluated two Caucasian populations (US and Italian) of men and women with PHPT, matched for age and body mass index (BMI), in a cross-sectional retrospective observational study. METHODS: We studied 74 US (23 men) and 126 Italian (42 men) patients evaluating main biochemical indices of the disease and bone mineral density (BMD) at the spine and proximal femur. RESULTS: Mean serum calcium levels were higher both in Italian men compared to women (11.7 ± 1.22 mg/dl and 11.1 ± 0.83, p<0.01) and in Italian compared to US patients (11.3 ± 1.01 and 10.8 ± 0.58, p<0.001), with similar results for the serum ionized calcium. Mean serum PTH levels were not different either between the genders or between the countries. After controlling for BMI, the mean BMD at both the femoral neck and total hip in females US patients was significantly higher compared with Italian female patients. CONCLUSION: Despite similar levels of circulating PTH, Italian patients have more pronounced effects of the disease as assessed by serum calcium and a more significant cortical involvement in women as assessed by BMD.

Consumption of healthy foods at different content of antioxidant vitamins and phytochemicals and metabolic risk factors for cardiovascular disease in men and women of the Moli-sani study.

BACKGROUND/OBJECTIVES: To categorize healthy food groups into categories of low-antioxidant (LAC) or high-antioxidant vitamins and phytochemicals content (HAC) and comparatively associate them with metabolic risk factors for cardiovascular disease (CVD). SUBJECTS/METHODS: A total of 6879 women (55±12 years) and 6892 men (56 ± 12 years) were analyzed from the Moli-sani cohort, randomly recruited from the general population. The European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary assessment. The antioxidant content of each food group was evaluated using Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione and United States Department of Agriculture (USDA) food composition tables. Healthy foods, according to a Mediterranean dietary pattern, were categorized into HAC or LAC; total food antioxidant content (FAC) score was constructed for a comparative evaluation of the consumption of these two groups. RESULTS: In men, an increase in FAC score, which represents an increased consumption of HAC with respect to LAC foods, was associated with a decrease in systolic blood pressure, diastolic blood pressure and C-reactive protein (CRP) (ß=-0.5, P=0.02, ß=-0.3, P=0.02 and ß=-0.03, P=0.03, respectively). Logistic regression analyses showed that in men 15% (30 units) increase in FAC score was associated with 6% decrease in the likelihood of having hypertension (odds ratio (OR)=0.94, 95% confidence interval (CI) 0.91-0.98) and 3% decrease in the likelihood of having a high CRP risk level (OR=0.97, 95% CI 0.94-0.99). No significant associations were observed in women. CONCLUSIONS: A possible greater protective role of healthy HAC as compared with healthy LAC foods on hypertension and inflammation was detected in men. These results stress the importance of studying healthy foods according to their content in antioxidant vitamins and phytochemicals, in primary prevention of CVD.

Typical breakfast food consumption and risk factors for cardiovascular disease in a large sample of Italian adults.

BACKGROUND AND AIMS: The overall consumption of foods most frequently consumed in a typical Italian breakfast might be associated with a better cardiovascular risk profile in Italian adults. METHOD SAND RESULTS: 18,177 subjects (53,2% women), aged ≥ 35 yrs, randomly selected from the Moli-sani Project population were studied. The European Prospective Investigation into Cancer and Nutrition (EPIC) FFQ was used for dietary assessment. To derive breakfast pattern, an "a priori" approach was used: firstly, foods typical of the Italian breakfast were selected: milk, coffee, tea, yogurt, crispbread/rusks, breakfast cereals, brioche, biscuits, honey, sugar and jam. The breakfast score was obtained adding the amounts of all selected foods, expressed in grams/day, previously standardized to mean zero and standard deviation 1. Subjects showing a higher breakfast score appeared to be younger, more frequently women or smokers, with higher social status but less likely practicing physical activity. After multivariable analyses, subjects with a higher breakfast food consumption had a lower risk to have high body mass index, abdominal obesity, systolic and diastolic blood pressure, blood glucose, triglycerides, total cholesterol (P < 0.0001 for all) and C Reactive Protein (P = 0.022). The associations were unrelated to age, sex, smoking, obesity, physical activity and social status. Subjects with a higher food breakfast score also showed a better physical healthy status score, a lower risk of metabolic syndrome (OR = 0.63; 0.55-0.72 95% CI) and of future CVD (P < 0.0001 for both women and men). CONCLUSION: Consumption of typical Italian breakfast foods positively affects CVD risk profile in an adult Italian population.

Sporadic and hereditary primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, particularly frequent in post-menopausal women. It is characterized by hypercalcemia with inappropriately high spontaneous plasma PTH. Singlegland adenoma is the most common cause (75- 85%). PHPT is usually a sporadic disease but in approximately <5% of cases, a familial hyperparathyroid syndrome is diagnosed. Familial hyperparathyroidism is a clinically and genetically heterogeneous group of disorders including: multiple endocrine neoplasia (MEN) type 1, MEN type 2A, MEN4, benign familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, hyperparathyroidism-jaw tumor syndrome, and familial isolated hyperparathyroidism. These syndromes show mendelian inheritance patterns and the main genes for most of them have been defined. The classic form of PHPT, which presents with hypercalcemia, kidney stones, and bone disease, is no longer common. Currently, there is an increasing interest in the subtle manifestations of PHPT, particularly the cardiovascular and neuropsychiatric manifestations. Parathyroidectomy is the definitive cure for PHPT even though patients with the asymptomatic form of the disease can be followed conservatively.

Extended criteria liver donation and transplant recipient consent: the European experience.

The organization known as ELPAT (Ethical, Legal and Psychological Aspects of Organ Transplantation) coordinated the distribution of an electronic questionnaire concerning the definition of extended criteria liver donation (ECD) and the implication for informed consent of transplant recipients to European liver transplant centers. Completed questionnaires were received from 30 centers in 13 countries. Twenty-eight centers accepted ECD liver donors. The criteria for defining a liver donor as ECD were: steatosis in 24 centers (85%); age up to 80 years in 23 centers (82%); serum sodium levels higher than 165 mmol/L in 17 centers (60%); intensive care unit stay with ventilation longer than 7 days in 16 centers (57%); serum glutamic oxalo-acitic transaminase levels higher than 90 U/L in 12 centers (42%); body mass indeces more than 30 in 10 centers (35%); serum glutamic pyruvic transaminase levels higher than 105 U/L in 10 centers (35%); serum bilirubin levels higher than 3 mg/dL in 10 centers (35%); and other criteria in 13 centers (46%). Twenty-three centers informed the transplant candidate of the ECD status of the donor: 10 centers (43%) when the patient registered for transplantation, 3 centers (14%) when an ECD liver became available, and 10 centers (43%) on both occasions. Ten centers required the liver transplant candidate to sign a special consent form. Ten centers informed the potential recipient of the donor's serology. Only three centers informed the potential recipient of any high risk behavior of the donor.

Laser-self-mixing interferometry in the Gaussian beam approximation: experiments and theory.

We analyze the laser-self-mixing process in the Gaussian beam approximation and reformulate the expression of the feedback coefficient C in terms of the effective feedback power coupled back into the laser diode. Our model predicts a twenty-fold increase of the ratio between the maximum and the minimum measurable displacements judged against the current plane-wave model. By comparing the interaction of collimated or diverging Gaussian laser beams with a plane mirror target, we demonstrate that diverging beams tolerate larger wobbling during the target displacement and allow for measurement of off-axis target rotations up to the beam angular width. A novel method for reconstructing the phase front of the Gaussian beam by self-mixing scanning measurements is also presented.

A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated.

Local recurrences after breast conserving surgery occur mostly in the quadrant harbouring the primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area, while irradiation of the whole breast may be avoided. We have developed a new technique of intra-operative radiotherapy (IORT) of a breast quadrant after the removal of the primary carcinoma. A mobile linear accelerator (linac) with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Through a perspex applicator, the radiation is delivered directly to the mammary gland and to spare the skin from the radiation, the skin margins are stretched out of the radiation field. To protect the thoracic wall, an aluminium-lead disc is placed between the gland and the pectoralis muscle. Different dose levels were tested from 10 to 21 Gy without important side-effects. We estimated that a single fraction of 21 Gy is equivalent to 60 Gy delivered in 30 fractions at 2 Gy/fraction. Seventeen patients received a dose of IORT of 10 to 15 Gy as an anticipated boost to external radiotherapy, while 86 patients received a dose of 17-19-21 Gy intra-operatively as their whole treatment. The follow-up time of the 101 patients varied from 1 to 17 months (mean follow-up time was 8 months). The IORT treatment was very well accepted by all of our patients, either due to the rapidity of the radiation course in cases where IORT was given as the whole treatment or to the shortening of the subsequent external radiotherapy in cases where IORT was given as an anticipated boost. We believe that single dose IORT after breast resection for small mammary carcinomas may be an excellent alternative to the traditional postoperative radiotherapy. However, a longer follow-up is needed for a better evaluation of the possible late side-effects.

Subnuclear localization and mitotic phosphorylation of HIRA, the human homologue of Saccharomyces cerevisiae transcriptional regulators Hir1p/Hir2p.

The HIRA gene encodes a nuclear protein with histone-binding properties that have been conserved from yeast to humans. Hir1p and Hir2p, the two HIRA homologues in Saccharomyces cerevisiae, are transcriptional co-repressors whose action resides at the chromatin level and occurs in a cell-cycle-regulated fashion. In mammals, HIRA is an essential gene early during development, possibly through the control of specific gene-transcription programmes, but its exact function remains to be deciphered. Here we report on the subnuclear distribution and cell-cycle behaviour of the HIRA protein. Using both biochemical and immunofluorescence techniques, a minor fraction of HIRA was found tightly associated with the nuclear matrix, the material that remains after nuclease treatment and high-salt extraction. However, most HIRA molecules proved extractable. In non-synchronized cell populations, extraction from chromatin necessitated 300 mM NaCl whereas 150 mM was sufficient in mitotic cells. Immunofluorescence staining and microscopic examination of mitotic cells revealed HIRA as excluded from condensed chromosomes, confirming a lack of association with chromatin during mitosis. Western-blot analysis indicated that HIRA molecules were hyper-phosphorylated at this point in the cell cycle. Metabolic labelling and pulse-chase experiments characterized HIRA as a stable protein with a half-life of approx. 12 h. The mitotic phosphorylation of HIRA could provide the dividing cell with a way to retarget HIRA-containing multi-protein complexes to different chromatin regions in daughter compared with parental cells.

Millimeter-wave time-resolved studies of HCO+-H2 inelastic collisions.

A novel ion cell has been constructed for the purpose of studying rotationally inelastic collisions involving truly thermal molecular ions at low temperatures. With this ion cell, time-resolved double resonance (pump-probe) spectroscopic experiments have been performed to determine the cross sections for relaxation of the J = 2 state of HCO+ in collisions with normal-H2 at temperatures around 40 and 77 K. The HCO+ is pumped through the J = 2<--1 transition and probed via the J = 3<--2 transition. The cross sections at the lower temperature are slightly below those predicted by the simple Langevin theory, while those at the higher temperature are in good agreement with this theory.