Effects of maternal protein restriction during pregnancy and lactation on milk composition and offspring development.

Before weaning, breast milk is the physiological form of neonatal nutrition, providing pups with all nutrient requirements. Maternal low-protein diet (LPD) during pregnancy and lactation induces adverse changes in key maternal organs, which have negative effects on pup development. We studied the effects of maternal LPD on liver weight, mammary gland (MG) cell differentiation, milk composition and production and pup development throughout lactation. We fed rats with control (C) or LPD (R) during pregnancy and lactation. At 7 d early, 14 d mid and 21 d late lactation stages, maternal biochemical parameters, body, liver and MG weights were analysed. MG cell differentiation was analysed by haematoxylin and eosin staining; milk nutrient composition and production were studied; pup body, liver and brain weights, hippocampal arachidonic acid (AA) and DHA were quantified. Results showed lower body and liver weights, minor MG cell differentiation and lower serum insulin and TAG in R compared with C. R milk contained less protein and higher AA at early and mid stages compared with C. R pup milk and fat intake were lower at all stages. R protein intake at early and mid stages and DHA intake at mid and late stages were lower compared with C. In R pups, lower body, liver and brain weights were associated with decreased hippocampal AA and DHA. We conclude that maternal LPD impairs liver and MG function and induces significant changes in maternal milk composition, pup milk intake and organ development.

Expression-based, consistent biomarkers for prognosis and diagnosis in lung cancer.

OVERVIEW: Lung cancer is one of the deadliest cancers in the world. Its histological classification depends on early diagnosis and successful treatment. Therefore, having specific biomarkers for a quick sorting widens the successful output of lung cancer treatment. MATERIAL AND METHODS: High-throughput sequencing (RNA-seq) was performed of small cohorts of BioBanco samples from healthy and tumour cells from lung adenocarcinoma (LUAD) and squamous cell carcinoma of the lung (lSCC). RNA-seq samples from small cell lung cancer (SCLC) were downloaded from databases. A bioinformatic workflow has been programmed for the identification of differentially expressed genes (DEGs). RESULTS: A total of 4777 DEGs were differentially expressed in SCLC, 3676 DEGs were in lSCC, while the lowest number of DEGs, 2819, appeared in LUAD. Among them, 945 DEGs were common to the three histological types. Once validated their expression profile and their survival predictive capacity in large, public cohorts, three DEGs can be exclusively considered as diagnostic biomarkers, three as prognosis biomarkers, and other three exhibit both diagnosis and prognosis capabilities. CONCLUSIONS: This prospective study presents evidences for the diagnostic and prognostic capabilities of expression changes in CAPN8-2, TMC5 and MUC1 in LUAD, while they are non-significant in SCLC and lSCC. Their translation to clinical practice is proposed.

Experimental verification of a non-invasive method to monitor the lateral pencil beam position in an anthropomorphic phantom for carbon-ion radiotherapy.

The dose conformation and the sparing of neighboring critical healthy structures are improved in carbon-ion beam radiotherapy in comparison to conventional photon radiotherapy. Inter and intrafractional plan adaptation strategies may preclude the quality assurance (QA) of the actually applied treatment plan before the treatment starts. Therefore, independent measurements of the positions of scanned pencil 12C ion beams are of interest in order to monitor the beam application during the treatment and the beam in the isocenter. In this work, secondary ions outgoing from a patient-like phantom are exploited for the assessment of the lateral pencil beam position in a clinic-like 12C treatment fraction. The experiment was performed at the Heidelberg Ion-Beam Therapy Center (HIT) in Germany. A carbon-ion treatment plan was used to treat a 100 cm3 tumor volume in the center of an Alderson head phantom. Two silicon pixel detectors based on the Timepix3 technology developed at CERN were operated in synchronization to detect and to track outgoing secondary ions. We established an analysis of the measured secondary ion track distribution which enabled us to follow the beam scanning movement of the carbon-ion pencil beam by assessing the lateral position of the single beam spots. The precision of the developed method was found to range from 0.84 mm to 2.59 mm. For beam energies greater than 197.58 MeV/n, the mean of absolute distances of the measured lateral pencil beam positions with respect to the pencil beam positions measured by the beam application system (averaged over each energy layer) were smaller than 2 mm. We conclude that the presented method has shown capabilities of monitoring the lateral pencil beam positions by means of secondary ions with precision and sensitivity of clinical interest.

Data-intensive Undergraduate Research Project Informs to Advance Healthcare Analytics.

The overarching framework for incorporating informatics into the Wesley College (Wesley) undergraduate curriculum was to teach emerging information technologies that prepared undergraduates for complex high-demand work environments. Federal and State support helped implement Wesley's undergraduate Informatics Certificate and Minor programs. Both programs require project-based coursework in Applied Statistics, SAS Programming, and Geo-spatial Analysis (ArcGIS). In 2015, the State of Obesity listed the obesity ranges for all 50 US States to be between 21-36%. Yet, the Center for Disease Control and Prevention (CDC) mortality records show significantly lower obesity-related death-rates for states with very high obesity-rates. This study highlights the disparities in the reported obesity-related death-rates (specified by an ICD-10 E66 diagnosis code) and the obesity-rate percentages recorded for all 50 US States. Using CDC mortality-rate data, the available obesity-rate information, and ArcGIS, we created choropleth maps for all US States. Visual and statistical analysis shows considerable disparities in the obesity-related death-rate record-keeping amongst the 50 US States. For example, in 2015, Vermont with the sixth lowest obesity-rate had the highest reported obesity-related death-rate. In contrast, Alabama had the fifth highest adult obesity-rate in the nation, yet, it had a very low age-adjusted mortality-rate. Such disparities make comparative analysis difficult.

Advances in the development of molecular tools for the control of bovine babesiosis in Mexico.

The severe negative impact that bovine babesiosis has in the Mexican cattle industry has not been ameliorated basically due to the lack of safe and effective commercially available vaccines and sensitive and reliable diagnostic tests. In recent years, the Bovine Babesiosis Laboratory at the National Center for Disciplinary Research in Veterinary Parasitology-INIFAP in Morelos State, Mexico has been directing efforts towards three main research areas: (1) The development of in vitro culture-derived, improved and safer live vaccines. This has been done in two ways: using gamma-irradiated bovine serum and erythrocytes for the in vitro culture of vaccine strains, which reduces the risk of contaminating pathogens, and improving the immune response, by the addition of L. casei, a strong stimulant of the innate immune system. (2) The study of antigens considered as vaccine candidates with the goal of developing a recombinant vaccine that suits the country's needs. Knowing their degree of conservation or variation in Mexican isolates, their phylogenetic relationship and their protective, immuno-stimulatory properties, are first steps towards that goal. (3) The development of new tools for diagnosis, detection and discrimination of bovine babesiosis is the third area. Developing variants of ELISA, which are more reliable than the currently used IFAT, are a priority, and finally, taking advantage of the genomes of Babesia bigemina, and B. bovis, we are identifying genes than allow us to discriminate isolates using molecular tools.

Hemopoietic-specific Sf3b1-K700E knock-in mice display the splicing defect seen in human MDS but develop anemia without ring sideroblasts.

Heterozygous somatic mutations affecting the spliceosome gene SF3B1 drive age-related clonal hematopoiesis, myelodysplastic syndromes (MDS) and other neoplasms. To study their role in such disorders, we generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, the commonest type of SF3B1 mutation in MDS. Sf3b1K700E/+ animals had impaired erythropoiesis and progressive anemia without ringed sideroblasts, as well as reduced hematopoietic stem cell numbers and host-repopulating fitness. To understand the molecular basis of these observations, we analyzed global RNA splicing in Sf3b1K700E/+ hematopoietic cells. Aberrant splicing was associated with the usage of cryptic 3' splice and branchpoint sites, as described for human SF3B1 mutants. However, we found a little overlap between aberrantly spliced mRNAs in mouse versus human, suggesting that anemia may be a consequence of globally disrupted splicing. Furthermore, the murine orthologues of genes associated with ring sideroblasts in human MDS, including Abcb7 and Tmem14c, were not aberrantly spliced in Sf3b1K700E/+ mice. Our findings demonstrate that, despite significant differences in affected transcripts, there is overlap in the phenotypes associated with SF3B1-K700E between human and mouse. Future studies should focus on understanding the basis of these similarities and differences as a means of deciphering the consequences of spliceosome gene mutations in MDS.

Transcriptomic profiles of the upper olfactory rosette in cultured and wild Senegalese sole (Solea senegalensis) males.

The aims of this study were the characterization of the upper olfactory epithelium of cultured and wild Senegalese sole mature males at histological and transcriptomic (using RNA-Seq) level. No significant differences in tissue structure, cell types and cellular distribution pattern (olfactory sensory neurons) were identified between cultured and wild specimens. Deep transcriptomic analysis showed 2387 transcripts were differentially expressed between cultured and wild groups. A detailed analysis identified the differentially expressed transcripts included some olfactory receptors (OR, TAAR and V2R-like) and transcripts related with the control of reproduction such as the brain aromatase cytochrome P450 and tachykinin-3. Also a wide set of genes related with lipid sensing, metabolism and transport were differentially expressed and these transcripts were often down-regulated in cultured fish. Furthermore, cultured males presented a higher expression of genes related with goblet cells and mucin production that modulates innate and adaptive immune responses. All these changes in gene expression could be explained by different nutritional status and diet preference. The different expression of transcripts related to olfaction, reproduction, nutrient sensing and immune system demonstrate distinct differences in functionalities between cultured and wild soles providing new clues about the sexual dysfunction in this species.

Correlation of Allograft Weight to Recipient Body Weight Index on Renal Function in Kidney Transplantation.

BACKGROUND: The function of renal transplant grafts can be modified by many factors. In one study of graft weight/weight of the recipient, it was concluded to avoid renal transplantation in patients with kidneys with a low ratio between the graft and recipient weight (<2.5 g/kg). OBJECTIVE: The objective of this study was to describe the association between renal allograft weight and renal function 1 month after renal transplantation in the Mexican population. MATERIAL AND METHODS: We studied patients who underwent transplantation from living or cadaveric donors with 1 month of follow-up with a functioning graft. An observational, retrospective, analytic study from January 1, 2014 to November 1, 2014 was conducted. Graft weight, donor weight, recipient weight, age, donor gender, recipient creatinine, and renal function were recorded. RESULTS: A total of 88 patients were included: 35 women (39.8%) and 53 men (60.2%). Sixty (68%) received kidneys from living donors and 28 (31.8%) from deceased donors. Mean recipient body mass index (BMI) was 24.7 (±2.6). Mean graft weight was 152 g (±33.9). Creatinine at 1 month post-transplantation was 1.6 mg/dL (±2.0). Using a linear regression model cold ischemia time was related to serum creatinine at 1 month post-transplantation (P = .020). Using multivariate analysis, significance was observed with respect to these indexes and recipient renal function. Recipient gender also was related and showed statistical significance (P = .015). CONCLUSIONS: Renal graft function depends on many factors including the amount of functional renal mass and nephrons required according to the recipient's weight. The donor kidney weigt (DKW) / receptor body weigt (RBW) index should be considered as selection criteria of donors.

EEG findings in frontal lobe epilepsies.

As a group, epilepsies of frontal lobe origin are thought to be poorly localized using surface EEG recordings. This finding may depend on the specific areas of frontal lobe from which the seizures originate or the pathologic substrate. We reviewed the presurgical surface EEGs of patients with frontal lobe epilepsy who underwent epilepsy surgery. The specific area of the frontal lobe where seizures originated was determined by 1) intracranial ictal EEG recordings, or 2) the presence of a structural lesion, identified by imaging studies in patients who achieved complete seizure control following surgery. We differentiated patients whose seizures began in the dorsolateral frontal convexity from those whose seizures began in the medial frontal region, and we correlated EEG findings in the interictal, postictal, and ictal states with seizure semiology, pathologic substrate, and surgical outcome. Four of nine patients had seizures originating in the dorsolateral frontal convexity and five had medial frontal onset seizures. Patients whose seizures originated from the dorsolateral convexity had focal interictal epileptiform abnormalities that localized to the region of seizure onset. Patients whose seizures began in the medial frontal region had either no interictal epileptiform abnormality or had multifocal epileptiform discharges. Patients whose seizures began in the dorsolateral convexity showed focal electrographic seizure activity that was localizing. This rhythmic fast activity did not appear to be substrate-specific. Patients whose seizure onset localized to the medial frontal region did not show focal electrographic seizure at clinical onset. We conclude that the scalp EEG recordings of frontal lobe epilepsies contain features that enable differentiation of seizures originating from two different regions of the frontal lobe.

Voltage sensitivity response of ultrasonic hydrophones in the frequency range 0.25-2.5 MHz.

Frequency responses of different PVDF polymer hydrophones, including membrane and needle designs, were measured and are presented in terms of end-of-cable voltage sensitivity vs. frequency over a wide, 4.5-octave bandwidth ranging from 0.25-2.5 MHz. The experimental data indicate that the membrane PVDF hydrophones can exhibit uniform, to within +/- 0.75 dB, responses. However, a widely used bilaminar membrane hydrophone-preamplifier combination may display sensitivity variations of +/- 2 dB. Also, even well-designed needle-type hydrophones show a more distinct sensitivity variation below 1 MHz that is on the order of 3-4 dB. The overall uncertainty of the calibration technique was estimated to be better than +/- 2 dB in the frequency range considered. The technique, which uses a combination of swept frequency chirp and reciprocity so that both the relative and absolute plots of sensitivity vs. frequency can be obtained, is also briefly described. The results of this work are important to implement procedures for adequate determination of the mechanical index of ultrasound (US) imaging devices. Mechanical index is widely accepted as a predictor of potential bioeffects associated with cavitation phenomena. Also, absolute calibration data are essential in development of therapeutic procedures based on the use of high-intensity focused ultrasound (HIFU), and in characterization of conventional therapeutic US applicators operating at frequencies below 1 MHz.

Multicomponent analysis: Comparison of various graphical and numerical methods.

The performance of several graphical (zero-crossing and derivative quotient spectra with standardized divisor) and numerical methods (MULTIC and PLS) for the resolution of binary and ternary mixtures of species is compared. Numerical methods were found to be specially suited to multicomponent analysis, particularly for mixtures containing more than two analytes with highly overlapped spectra. The results obtained by using the compared methods to analyse various synthetic mixtures of acetylsalicylic acid, caffeine and thiamine were quite consistent and errors in the simultaneous quantification of the analytes amounted to less than 5% in all instances.

Simultaneous spectrofluorimetric determination of europium, dysprosium, gadolinium and terbium using chemometric methods.

A spectrofluorimetric method for the simultaneous determination of dysprosium, europium, gadolinium and terbium in ternary and quaternary mixtures by the use of pyridine-2,6-dicarboxylic acid as a chelating agent was developed. The influence of chemical variables affecting the analytical reaction was evaluated. A partial least-squares procedure and PC Quant software were used to assess data obtained from a variable number of calibration solutions and wavelengths. The ensuing method was validated by applying it to the analysis of synthetic ternary (Eu-Dy-Tb) and quaternary mixtures (Eu-Dy-Gd-Tb) over the concentration ranges 60-550 mug Eu l(-1), 30-400 mug Dy l(-1) and 30-400 mug Tb l(-1) in the former, and 20-220 mug Eu l(-1), 20-235 mug Dy l(-1), 25-230 mug Gd l(-1) and 75-230 mug Tb l(-1) in the latter. The results obtained by using the two quantitation procedures are compared. The relative errors in the determinations were less than 8% in most cases.

Simultaneous spectrophotometric determination of drugs in pharmaceutical preparations using multiple linear regression and partial least-squares regression, calibration and prediction methods.

Two new methods for the simultaneous determination of acetylsalicylic acid, acetaminophen and caffeine based on total absorbance measurements and their processing by multiple linear regession and partial least-squares regression are proposed. The concentration ranges used to construct the calibration matrix were 4.0-12.0, 2.0-10.0 and 0.9-6.0 mug ml(-1) for acetylsalicylic acid, acetaminophen and caffeine respectively. The proposed methods were validated by using a set of synthetic sample mixtures and subsequently applied to the determination of the three active principles in three different pharmaceutical preparations.

Simultaneous determination of diazepam and pyridoxine in synthetic mixtures and pharmaceutical formulations using graphical and multivariate calibration-prediction methods.

Several methods are reported for the simultaneous determination of diazepam and pyridoxine: two graphical methods (zero-crossing and derivative quotient spectra); and two numerical methods (multiple linear regression and partial least-squares regression). The methods have been applied in the concentration ranges 1.4-4.0 micrograms ml-1 diazepam and 4.0-12.0 micrograms ml-1 pyridoxine. The accuracy and precision of the methods have been determined and they have been validated by analysing synthetic mixtures containing the two drugs in variable proportions. The methods were also applied to the determination of diazepam and pyridoxine in pharmaceutical preparations. The analytical results were quite good in all cases.

Glaucomatous neurodegeneration and the concept of neuroprotection.

Glaucomatous neurodegeneration is a progressive pathological affair morphologically characterized by RGC death resulting in functional visual deterioration. Although a variety of primary insults ranging from mechanical trauma to ischemia to genetic susceptibility can initiate disease onset, apparently loss of trophic support and excitotoxin release remain the common themes responsible for neuronal damage and eventual cell death by apoptosis. The spread of this damage is perpetuated by secondary degeneration that allows directly injured neurons to release noxious and degenerative substances into the surrounding cells. Neuroprotection is a collective therapeutic approach the aim of which is to provide resilience to such neurons in an effort to prevent or delay progressive neuronal degeneration. At present, definitive neuroprotective therapy remains unachieved despite a variety of approaches having been defined and intensely pursued. However, the evolution in our understanding of glaucoma continues to offer reason for optimism. To this end, we remain unreservedly hopeful in the labor and committed work of dedicated investigators. We are all indebted to them.

Oral diseases and socio-economic status (SES).

OBJECTIVE: To determine the association between social, economic and behavioural risk factors and national prevalences of: oral cancer, dental caries (12-year-olds) and destructive periodontal disease (35-44-year-olds). DATA SOURCES: Sources for the social and economic parameters were the UN Development Program; the behavioural risk factors' source was the World Health Organization, the UN Food and Agricultural Organization and the World Atlas of History. Oral diseases data came from UICC Globocan and the World Health Organization databases. DATA EXTRACTION: Data were extracted by hand from official publications. DATA SYNTHESIS: Data were synthesized and analyzed in sequence using SPSS, Pearson's correlation coefficient and multiple regression analyses. CONCLUSIONS: There is a discernable association between the three oral diseases and the variables selected, which varies in strength, being strongest for chronic destructive periodontitis and weakest for oral cancer. Dental caries lies in between. The degree to which variables account for differences in the three oral diseases between the countries studied is striking, being insignificant for oral cancer incidence, modest for oral cancer mortality, stronger for dental caries and strongest for destructive periodontal disease. Removing variables with strong co-linearity with the Human Development Index has little effect on the regression coefficients.

Sensitivity of ultrasonic hydrophone probes below 1 MHz.

Frequency responses of different PVDF polymer hydrophone probes, including membrane and needle designs, were measured and are presented in terms of end-of-cable voltage sensitivity versus frequency over a wide, 4.5 octave bandwidth ranging from 0.25 to 2.5 MHz. The probes are seldom, if at all, characterized in this frequency range due to the difficulties associated with a lack of adequate and readily implementable calibration techniques. To this end, a technique, which uses a combination of swept frequency chirp and reciprocity, so that both the relative and absolute plots of sensitivity versus frequency can be obtained, was developed and tested. Salient features of the technique including the design of a 6 octave auxiliary acoustic source are described. The experimental data indicate that a majority of the PVDF membrane hydrophones exhibit a relatively uniform (to within +/- 2 dB) response. While, in general, this is not the case for commercially available needle hydrophone probes, it is evidenced that a careful attention to the PVDF probe design results in frequency characteristics fairly close to those achievable with a membrane design. The overall uncertainty of the calibration technique was estimated to be better than +/- 1.5 dB in the considered frequency range. The results of this work are important to implement procedures for adequate determination of the Mechanical Index (MI) of ultrasound imaging devices. MI is widely accepted as a predictor of potential bioeffects associated with cavitation phenomena. Current efforts are focused on extending the applicability of the technique to frequencies below 100 kHz.

Application of a low density support material as an alternative to prevent clogging in a three-phase fluidized-bed reactor.

A low density support material was evaluated to determine its effect on biofilm growth dynamics when treating synthetic wastewater in a three-phase fluidized-bed reactor. After two 40-day experimental runs, the results showed significant microbial activity from the very beginning of the study. The highest biofilm growth was observed during the first 10 days of operation. Biofilm kept gradually growing after the 11th day and reached a steady-state at day 21, defined by a consistent biomass attached to the particles. As an indicator of biofilm detachment effluent suspended biomass decreased as biofilm attachment increased, tending also to stabilize around day 21. During the first 10 days, chemical oxygen demand removal averaged 100 mg l(-1) representing 48% of the influent chemical oxygen demand concentration. The highest chemical oxygen demand removal efficiency (78%) was achieved between days 23 and 29, when influent chemical oxygen demand was 280 mg l(-1). The support material evaluated proved to be effective at allowing attachment of microorganisms. Due to its low density, bed fluidization was achieved under recirculation rates lower than those required to fluidize beds of higher density. The physical properties of the proposed support material allowed an appropriate equilibrium to be achieved between biomass attachment and detachment, eliminating the need for bed backwashing.

Reproducible model to perform kidney transplantation in a low-resource population.

BACKGROUND: In several countries, organ transplantation is limited. We describe the implementation of a model to perform kidney transplantation in a low-resource population through a financial mechanism sharing public, patient, and private foundations funds. METHODS: This was a cohort study of 100 low-resource patients undergoing renal transplantation at the Hospital General of México. The mean age of the transplanted population was 30.07 ± 11.4 years, from which 84% reported an income <400 USD/month. Ninety percent of grafts were obtained from live donors. RESULTS: The survival rate at 1 year after the procedure was 98%. Patient rehabilitation after transplantation included the incorporation of individuals into productive life and work. The economically active population increased from 8% to 40% after the transplant procedure. The model was successfully implemented as the result of (i) adequate incorporation of medical staff with solid experience in organ transplantation; (ii) institutional public policy and collaboration between diverse services to support donors and receptors; and (iii) financial collaboration to attract resources and funds to guarantee access to immunosuppressants. CONCLUSIONS: Our results led toward an operational, reproducible model for transplanting patients in developing and financial crisis countries, reflecting beneficial long-lasting effects on the patient from the therapeutic, clinical, and economic points of view.