Estudio de prefactibilidad para la instalación de una planta productora de hojuelas de maíz morado (Zea mays l.)

El objetivo del presente estudio es determinar la viabilidad de mercado, tecnológica, económica, financiera y social de la instalación de una planta de producción de hojuelas de maíz morado. El producto tendrá una presentación en bolsas de 200 gramos. El mercado meta será Lima Metropolitana, que representa el 32,6% de la población del Perú. A nivel de segmentación socioeconómica, los sectores elegidos son el A y el B. A nivel de segmentación conductual, se ha elegido a la generación Millenial (18 – 39 años) del sector A y B de Lima Metropolitana por su apertura a nuevos productos y estilo de vida. Esta generación representa el 36,88% de la población. El valor de venta a los distribuidores del canal moderno será de S/. 3,03 por bolsa, y el precio al consumidor final será de S/. 5,50 por bolsa de 200 gramos. La planta de producción se instalará en el distrito de Lurín en Lima Metropolitana, seleccionado por su ubicación adecuada con el proveedor y centros de distribución de los establecimientos del canal moderno. El tamaño de planta es de 71,75 kg/h de producto final. Por otro lado, la tecnología requerida para la elaboración de los productos es factible de adquirirse y emplearse. En cuanto a inversión, ésta asciende a S/. 2.291.744,12. Se consideró un financiamiento del 39% de la inversión, que incluye la construcción de la planta. El horizonte de la deuda es de 6 años, y 11,50% de tasa efectiva con cuotas crecientes. La evaluación económica establece S/1.032.096,94 de valor actual neto, 23,5% de tasa interna de retorno, 1,45 de relación beneficio-costo y un periodo de recupero de 5 años, 2 meses y 16 días. La evaluación financiera establece S/1.229.592,91 de valor actual neto, 31% de tasa interna de retorno, 1,88 de relación beneficio-costo y un periodo de recupero de 4 años, 11 meses y 3 días. Finalmente, en relación con la evaluación social, el valor agregado asciende a S/.12.109.122 y se logra una relación sobre inversión total de 5,28 soles por cada sol invertido.The objective of the present research is determinate the market, technical, economic, financial, and social viability for the installation of a purple corn flakes plant. The product will have a presentation in bags of 200 grams. The target market will be Metropolitan Lima, which represents 32,6% of the population of Peru. At the level of socioeconomic segmentation, the sectors chosen are A and B. At the level of behavioral segmentation, the Millennial generation (18 - 39 years old) from sector A and B of Metropolitan Lima have been chosen for their openness to new products and Lifestyle. This generation represents 36,88% of the population. The sale value to the modern channel distributors will be S /. 3,03 per bag, and the price to the final consumer will be S /. 5,50 per bag of 200 grams. The production plant will be installed in the district of Lurin in Metropolitan Lima, selected for its suitable location with the supplier and distribution centers of the supermarkets. The plant size is 71,75 kg / h of final product. On the other hand, the technology required to produce the products is feasible to acquire and use. Regarding investment, this amounts to S/. 2.291.744,12. A financing of 39% of the investment was considered, which includes the construction of the plant. The debt horizon is 6 years, and an effective rate of 11,50% with increasing installments. The economic evaluation establishes S/. 1.032.096,94 of net present value, 23,5% of internal rate of return, 1,45 of benefit-cost relation and a recovery period of 5 years, 2 months and 16 days. The financial evaluation establishes S/. 1.229.592,91 of net present value, 31% of internal rate of return, 1,88 of benefit-cost relation and a recovery period of 4 years, 11 months and 3 days. Finally, in relation to the social evaluation, the added value amounts to S/. 12.109.122 and a total investment ratio of 5.28 soles is achieved for each sol invested

AAV-mediated transcription factor EB (TFEB) gene delivery ameliorates muscle pathology and function in the murine model of Pompe Disease

Pompe disease (PD) is a metabolic myopathy due to acid alpha-glucosidase deficiency and characterized by extensive glycogen storage and impaired autophagy. We previously showed that modulation of autophagy and lysosomal exocytosis by overexpression of the transcription factor EB (TFEB) gene was effective in improving muscle pathology in PD mice injected intramuscularly with an AAV-TFEB vector. Here we have evaluated the effects of TFEB systemic delivery on muscle pathology and on functional performance, a primary measure of efficacy in a disorder like PD. We treated 1-month-old PD mice with an AAV2.9-MCK-TFEB vector. An animal cohort was analyzed at 3 months for muscle and heart pathology. A second cohort was followed at different timepoints for functional analysis. In muscles from TFEB-treated mice we observed reduced PAS staining and improved ultrastructure, with reduced number and increased translucency of lysosomes, while total glycogen content remained unchanged. We also observed statistically significant improvements in rotarod performance in treated animals compared to AAV2.9-MCK-eGFP-treated mice at 5 and 8 months. Cardiac echography showed significant reduction in left-ventricular diameters. These results show that TFEB overexpression and modulation of autophagy result in improvements of muscle pathology and of functional performance in the PD murine model, with delayed disease progression

The Titanium Surface Modulates the Expression of Beta-Catenin and DLX5 Genes in Pancreatic Ductal Carcinoma in Vitro. Can the Metallic Stent Increase PDAC Aggressiveness?

Context Adenoductal pancreas (PDAC) is a fatal cancer. Its aggressiveness is associated in part with the EMT process of metastasis. Two genes specifically involved in these phenomena are b-catenin and DLX5. While the first gene has been widely studied also in pancreatic cancer, few data are associated with DLX5. However, its over-expression has been recently associated with the formation of metastases in breast cancer in vivo. An exogenous factor involved in the modulation of the expression of these genes seems to be titanium. This compound is usually employed for the pallia action of patients with PDAC, to reduce choledochal stenosis due to compression. Objective The purpose of this study was to assess whether titanium is able to modulate the expression of these two genes in vitro. Methods We used a primary cell culture of PADC (PP78). The cells were seeded and cultivated in contact with two different titanium surfaces for 10 days. After this period the total mRNA was extracted and the quantification of β-catenin and DLX5 genes was performed by RT-PCR according to the ΔΔCt analysis. Then cells were stained using the immunofluorescence technique (IF) to quantify the b-catenin protein expression .using a computerized high-resolution acquisition system (D-Sight, Menarini, Florence, Italy) The cells were scored evaluating the cytoplasmic positivity as follows (0 absent, 1 low, 2 middle, 3 strong). The experiment was carried out in triplicate and untreated cells (without titanium contact) were used as control. Results Quantitative analyses showed that both titanium surfaces positively affected beta-catenin (mean 2.8 fold) and DLX5 (2.0 fold) mRNA expressions with respect to the controls (P<0.0007). Both titanium surfaces also increased the protein score 3 values of β-catenin in treated cells with respect to their controls (P=0.0158). Conclusion Our data showed that several titanium surfaces positively modulated the expression of two genes associated with the increase of the aggressiveness of PDAC in vitro. Clinical studies are needed to find out which type of stent can be used in the surgical operation with palliative intent

COVID-19 outbreak in Italy: an opportunity to evaluate extended interval dosing of ocrelizumab in MS patients

introduction during the COVID-19 pandemic, ocrelizumab (OCR) infusions for MS patients were often re-scheduled because of MS center's disruption and concerns regarding immunosuppression. The aim of the present study was to assess changes in OCR schedule during the first wave of pandemic in italy and to evaluate the effect of delayed infusion on clinical/radiological endpoints.methods data were extracted from the Italian MS register database. standard interval dosing was defined as an infusion interval <= 30 weeks, while extended interval dosing was defined as an infusion interval > 30 weeks at the time of the observation period. clinico-demographics variables were tested as potential predictors for treatment delay. time to first relapse and time to first MRI event were evaluated. Cumulative hazard curves were reported along their 95% confidence intervals. a final sample of one-thousand two patients with MS from 65 centers was included in the analysis: 599 pwMS were selected to evaluate the modification of OCR infusion intervals, while 717 pwRMS were selected to analyze the effect of infusion delay on clinical/MRI activity. results mean interval between two OCR infusions was 28.1 weeks before pandemic compared to 30.8 weeks during the observation period, with a mean delay of 2.74 weeks (p < 0.001). No clinico-demographic factors emerged as predictors of infusion postponement, except for location of MS centers in the north of italy. clinical relapses (4 in SID, 0 in EID) and 17 MRI activity reports (4 in SID, 13 in EID) were recorded during follow-up period. discussion despite the significant extension of OCR infusion interval during the first wave of pandemic in Italy, a very small incidence of clinical/radiological events was observed, thus suggesting durable efficacy of OCR, as well as the absence of rebound after its short-term suspension

Quality of care provided by Multiple Sclerosis Centers during Covid-19 pandemic: Results of an Italian multicenter patient-centered survey

Background: Covid-19 pandemic impacted on management of people with Multiple Sclerosis (pwMS). Level of satisfaction of pwMS regarding the care received by the staff of Multiple Sclerosis Centers (MSCs) during the pandemic was not fully investigated. In a large patient-centered multicenter study, the therapeutic adherence and quality of care of MSCs was assessed. Methods: In April-May 2021, an online survey was widespread by 16 Italian MSCs. Frequencies, percentages and/or means and standard deviations were calculated to describe the sample. ANOVAs were performed to evaluate the effect of sociodemographic and clinical variables on overall pwMS' rating of MSC assistance. Results: 1670 pwMS completed the survey (67.3% women). During the pandemic, 88% did not change their disease modifying therapy schedule, and 89.1% reached their MSCs with no or little difficulties. Even if only 1.3% of participants underwent a tele-health follow-up visit with their MSC staff, the 80.1% believed that tele-health services should be improved regardless of pandemic. 92% of participants were satisfied of how their MSC took charge of their needs; ANOVAs revealed an effect of disease duration on pwMS' level of satisfaction on MSCs management during the pandemic. Conclusions: The results revealed an efficient MSCs response to Covid-19 pandemic and provided the basis for the implementing of tele-health services that would further improve the taking charge of patients, particularly those with longer disease, higher disability, and/or living far from their MSC

Integrin Beta 1 Is Crucial for Urinary Concentrating Ability and Renal Medulla Architecture in Adult Mice

Integrins are heterodimers anchoring cells to the surrounding extracellular matrix (ECM), an active and complex process mediating a series of inside-out and outside-in stimuli regulating cellular turn-over, tissue growth and architecture. Itgb1 is the main subunit of the renal integrins and it is critical for renal development. This study aims to investigate the role of Itgb1 in the adult renal epithelial cells by knocking down Itgb1 in PAX8 expressing cells. Itgb1-Pax8 cKO mice develop a progressively worsening proteinuria and renal abnormalities leading to severe renal failure and hypertension. This phenotype is also associated with severe dysfunction of distal nephron and polyuria. To further investigate whether distal nephron involvement was primarily related to Itgb1 suppression or secondary to renal failure, an Itgb1-AQP2 cKO mouse model was generated. These mice lack Itgb1 expression in AQP2 expressing cells. They do not show any developmental alteration, but 1 month old mice are resistant to dDAVP administration and finally, at 2 months of age, they develop overt polyuria. This phenotype is due to primary collecting duct (CD) cells anoikis. The entire architecture of the outer medulla is altered, with loss of the typical organization pattern of vascular and tubular bundles alternation. Indeed, even though not primarily affected by genetic ablation, the TAL is secondarily affected in this model. It is sufficient to suppress Itgb1 expression in the CD in order to stimulate proliferation and then disappearance of neighboring TAL cells. This study shows that cell to cell interaction through the ECM is critical for architecture and function maintenance of the outer medulla and that Itgb1 is crucial for this process

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon