Safety and immunogenicity of heterologous COVID-19 vaccine regimens to deal with product shortage: A randomised clinical trial in an elderly population.

Objectives: In a context of COVID-19 vaccine shortages, this study sought to evaluate the safety and efficacy of receiving one dose of Gam-COVID-Vac rAd26 followed by a second COVID-19 vaccine dose of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV in a cohort of older adults. Study design: Single-centre, randomised, open label, non-inferiority trial. Methods: Adults aged ≥65 years who had received one dose of Gam-COVID-Vac rAd26 were randomised in a 1:1:1 ratio to receive a second-dose COVID-19 vaccination of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV. The primary outcome was the assessment of the humoral immune response to vaccination (i.e. antibody titres of SARS-CoV-2 spike protein at 28 days after second-dose vaccination). In addition, neutralising antibody titres at day 28 for the three schedules were measured. Results: Of 85 participants who were enrolled in the study between 26 and July 30, 2021, 31 individuals were randomised to receive Gam-COVID-Vac rAd5, 27 to ChAdOx1 nCoV-19 and 27 to BBIBP-CorV. The mean age of participants was 68.2 years (SD 2.9) and 49 (57.6%) were female. Participants who received Gam-COVID-Vac rAd5 and ChAdOx1 nCoV1-19 showed significantly increased anti-S titres at 28 days after second-dose vaccination, but this magnitude of difference was not observed for those who received BBIBP-CorV. The ratio between the geometric mean at day 28 and baseline within each group was 11.8 (6.98-19.89) among patients assigned to Gam-COVID-Vac rAd26/rAd5, 4.81 (2.14-10.81) for the rAd26/ChAdOx1 nCoV-19 group and 1.53 (0.74-3.20) for the rAd26/BBIBP-CorV group. All of the schedules were shown to be safe. Conclusions: The findings in this study contribute to the scarce information published on the safety and immunogenicity of Gam-COVID-Vac heterologous regimens and will help the development of guidelines and vaccine programme management.

Psychosocial and biological predictors of resident physician burnout.

BACKGROUND: A high proportion of health professionals in training suffer from work-related stress and may develop a burnout syndrome. OBJECTIVES: To study the incidence of burnout after the first year of residency in a teaching hospital and to identify baseline psychological, psychosocial work conditions, and biological risk factors. METHODOLOGY: We assessed the following in a prospective cohort of residents at baseline (first month residence) and after 1 year: background factors (socio-demographics, psychiatric history), perceived stress score (Perceived Stress Scale), Maslach Burnout Inventory score, and psychosocial factors (Job Content Questionnaire). Blood samples were obtained to study serum cortisol, IL-6, and TNF-α concentrations. The cumulative incidence was modelled by multivariate log-binomial regression analysis. RESULTS: We included 71 participants with a female majority (64.8%), age 26.4 (2.65) years, psychiatric history in 20%, and burnout in 13%. Among those without burnout initially (N = 59), it had developed by 1 year in 22% of residents. Increased job demand (RR = 1.259, 95%CI = 1.019-1.556, p = 0.033) and decreased cortisol levels (RR = 0.877, 95%CI = 0.778-0.989, p = 0.032) predicted burnout after 1 year of residency among medical trainees. CONCLUSION: Burnout syndrome develops in 22% of residents by 1 year of training and can be predicted by increased work demands and decreased cortisol levels.

Real-time reflectance anisotropy spectroscopy of GaAs homoepitaxy.

Reflectance anisotropy spectroscopy (RAS) is a highly sensitive optical probe for the real-time study of the epitaxial growth of zincblende semiconductors. Here we report on (1) non-equilibrium RAS spectra acquired in real time during the homoepitaxial growth of GaAs, and (2) RAS spectra for GaAs surfaces under equilibrium with several arsenic overpressures. We show that in both cases RAS spectra can be decomposed into two basic components, each with a characteristic line shape. We further show that both dynamic and equilibrium RAS spectra are described by the same pair of basic components. We conclude that the time evolution of non-equilibrium RAS spectra acquired during the epitaxial growth can be described in terms of RAS spectra for equilibrium surfaces. The results reported here should be useful for the interpretation of the physics underlying the rapid time evolution of dynamic RAS spectra during the first monolayer growth. Thus, we show that RAS constitutes a valuable tool for the study of epitaxial growth mechanisms.

Sequence analysis of five exons of SLC6A4 gene in Mexican patients with anorexia nervosa and bulimia nervosa.

BACKGROUND: Accumulating evidence indicates that alterations in the serotonin system are related to changes in eating behavior. The serotonin transporter is encoded by the SLC6A4 gene and has been an interesting candidate for anorexia nervosa- restrictive type (AN-R) and bulimia nervosa (BN). Interestingly, functional variants have been identified in the coding region that could contribute to understand the role of this gene in eating disorders. The aim was to identify genetic variants in five exons of SLC6A4 gene using Sanger-sequencing in anorexia nervosa-restrictive and bulimia nervosa patients, and a control group. METHOD: The sample consisted of 86 patients and 50 control subjects. We obtained DNA samples from all subjects and performed Sanger-sequence analysis of the 1, 2, 3, 8 and 9 exons. The sequences were compared with the reference sequence of the SLC6A4 gene. RESULTS: The sequence analysis of the five exons of the gene identified several variants. In the AN-R, we observed two novel variants (g.130delA and c.1740G > A), three synonymous variants (rs57172732, rs55908624, rs74478645) and a missense variant (L90F) reporting a probably deleterious and damaging variant. In BN, we identified two novel variants (g.295C > G and c.1725G > A), and the non-synonymous (rs28914832/I425V), reported as benign. Interestingly, we observed the 425V variant in three patients in the BN, variant that previously was reported in patients with a spectrum obsessive-compulsive disorder. CONCLUSION: The results of our study suggest that variants of the SLC6A4 gene are related with a possible damaging or gain-of-function and may be involved in the susceptibility to AN-R and BN patients. However, the present findings should be considered as preliminary until replicated in large samples.

In vivo model to study the impact of genetic variation on clinical outcome of mastitis in uniparous dairy cows.

BACKGROUND: In dairy herds, mastitis causes detrimental economic losses. Genetic selection offers a sustainable tool to select animals with reduced susceptibility towards postpartum diseases. Studying underlying mechanisms is important to assess the physiological processes that cause differences between selected haplotypes. Therefore, the objective of this study was to establish an in vivo infection model to study the impact of selecting for alternative paternal haplotypes in a particular genomic region on cattle chromosome 18 for mastitis susceptibility under defined conditions in uniparous dairy cows. RESULTS: At the start of pathogen challenge, no significant differences between the favorable (Q) and unfavorable (q) haplotypes were detected. Intramammary infection (IMI) with Staphylococcus aureus 1027 (S. aureus, n = 24, 96 h) or Escherichia coli 1303 (E. coli, n = 12, 24 h) was successfully induced in all uniparous cows. This finding was confirmed by clinical signs of mastitis and repeated recovery of the respective pathogen from milk samples of challenged quarters in each animal. After S. aureus challenge, Q-uniparous cows showed lower somatic cell counts 24 h and 36 h after challenge (P < 0.05), lower bacterial shedding in milk 12 h after challenge (P < 0.01) and a minor decrease in total milk yield 12 h and 24 h after challenge (P < 0.01) compared to q-uniparous cows. CONCLUSION: An in vivo infection model to study the impact of genetic selection for mastitis susceptibility under defined conditions in uniparous dairy cows was successfully established and revealed significant differences between the two genetically selected haplotype groups. This result might explain their differences in susceptibility towards IMI. These clinical findings form the basis for further in-depth molecular analysis to clarify the underlying genetic mechanisms for mastitis resistance.

Oxidative post-translational modifications controlling plant-pathogen interaction.

Pathogen recognition is linked to the perception of microbe/pathogen-associated molecular patterns triggering a specific and transient accumulation of reactive oxygen species (ROS) at the pathogen attack site. The apoplastic oxidative "burst" generated at the pathogen attack site depends on the ROS-generator systems including enzymes such as plasma membrane NADP (H) oxidases, cell wall peroxidases and lipoxygenase. ROS are cytotoxic molecules that inhibit invading pathogens or signalling molecules that control the local and systemic induction of defence genes. Post-translational modifications induced by ROS are considered as a potential signalling mechanism that can modify protein structure and/or function, localisation and cellular stability. Thus, this review focuses on how ROS are essential molecules regulating the function of proteins involved in the plant response to a pathogen attack through post-translational modifications.

Genetic selection for bovine chromosome 18 haplotypes associated with divergent somatic cell score affects postpartum reproductive and metabolic performance.

The susceptibility of animals to periparturient diseases has a great effect on the economic efficiency of dairy industries, on the frequency of antibiotic treatment, and on animal welfare. The use of selection for breeding cows with reduced susceptibility to diseases offers a sustainable tool to improve dairy cattle farming. Several studies have focused on the association of distinct bovine chromosome 18 genotypes or haplotypes with performance traits. The aim of this study was to test whether selection of Holstein Friesian heifers via SNP genotyping for alternative paternal chromosome 18 haplotypes associated with favorable (Q) or unfavorable (q) somatic cell scores influences postpartum reproductive and metabolic diseases. Thirty-six heifers (18 Q and 18 q) were monitored from 3 wk before calving until necropsy on d 39 (± 4 d) after calving. Health status and rectal temperature were measured daily, and body condition score and body weight were assessed once per week. Blood samples were drawn twice weekly, and levels of insulin, nonesterified fatty acids, insulin-like growth factor-I, growth hormone, and ß-hydroxybutyrate were measured. Comparisons between the groups were performed using Fisher's exact test, chi-squared test, and the GLIMMIX procedure in SAS. Results showed that Q-heifers had reduced incidence of metritis compared with q-heifers and were less likely to develop fever. Serum concentrations of ß-hydroxybutyrate were lower and insulin-like growth factor-I plasma concentrations were higher in Q- compared with q-heifers. However, the body condition score and withers height were comparable between haplotypes, but weight loss tended to be lower in Q-heifers compared with q-heifers. No differences between the groups were detected concerning retained fetal membranes, uterine involution, or onset of cyclicity. In conclusion, selection of chromosome 18 haplotypes associated with a reduced somatic cell score resulted in a decreased incidence of postpartum reproductive and metabolic diseases in this study. The presented data add to the existing knowledge aimed at avoiding negative consequences of genetic selection strategies in dairy cattle farming. The underlying causal mechanisms modulated by haplotypes in the targeted genomic region and immune competence necessitate further investigation.

Clinico-pathological features of the intradiaphragmatic bronchogenic cysts: report of a case and review of the literature.

Bronchogenic cysts represent congenital malformations deriving from an abnormal development of the primitive foregut during embryogenesis. These lesions are rarely found and they are most frequently localized in the mediastinum, or in lung parenchyma. Intramuscular localization is extremely rare, especially within the diaphragm. We report a case of a 54 year old man showing a large lobulated cystic lesion in the left hemidiaphragm. Complete surgery was performed and histological diagnosis of intradiaphragmatic bronchogenic cyst was made during surgery and confirmed after a total section analysis. Moreover we reviewed the other cases published in the English literature, including clinical, surgical and pathological data.

Assessment of the Renal Function in Potential Donors of Living Kidney Transplants: Expanded Study.

INTRODUCTION: It is very important to determine as accurately as possible the renal function in potential living renal transplant donors, especially those with limited renal function (CrCl <90 mL/m/1.73 m(2)), age older than 50 years, and cardiovascular risk factors that might favor the development of long-term kidney diseases. OBJECTIVE: The objective of this study was to compare the direct measurement of glomerular filtration rate (GFR) using EDTA-Cr51 and the estimations based on creatinine (eGFR): Cr clearance (CCr) with 24-hour urine and estimated using Cockroft-Gault (adjusted by using body surface area-Mosteller formula-SC), MDRD-4, MDRD-6, and CKD-EPI to determine the usefulness of different methods from EDTA-Cr51to evaluate the kidney function. PATIENTS AND METHODS: The kidney function evaluation has been made to 105 potential kidney donors using the EDTA-Cr51 method. The GFR obtained through the EDTA-Cr51 is compared with the CCr values in 24-hour urine and eGFR based on creatinine (Cockcroft-Gault, MDRD4, MDRD6, and CKD-EPI). RESULTS: Using the Bland Altman graphic we have observed that the most dispersed results are obtained with the eGFR using CCr in 24-hour urine and CKD-EPI. By means of Pasing & Bablock, we realized that MDRD-4 and MDRD-6 show the highest approximation to the reference method proposed to be substituted, whereas CCr shows a high dispersion. CONCLUSIONS: eGFR using MDRD-4 and MDRD-6 formulas reveal the best adjustment to the measure by EDTA-Cr51. This might represent the best option if a direct eGFR measure is not available.

Study of renal function in living kidney donors: estimated or measured glomerular filtration.

INTRODUCTION: In living kidney donations the accuracy of renal function is fundamental, especially for potential donors who have limited renal function (creatinine clearance levels [CCr] <90 mL/m/1.73 m(2)), are >50 years old, and who have cardiovascular risk factors that might favor the development of kidney diseases. OBJECTIVE: To compare the direct measured glomerular filtration (mGFR) using 51Cr-EDTA and the estimations based on creatinine (estimated glomerular filtration rate [eGFR]): CCr with 24-hour urine, and estimated using Cockroft-Gault (adjusted using body surface area, Mosteller formula), modification of diet in renal disease-4 (MDRD-4), MDRD-6, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) to determine the usefulness of different methods to evaluate the kidney function. PATIENTS AND METHODS: The kidney function evaluation was performed for 37 potential kidney donors using the 51Cr-EDTA method. The GFR obtained through the 51Cr-EDTA was compared with the CCr values in 24-hour urine and eGFR based on creatinine (Cockcroft-Gault, MDRD-4, MDRD-6, and CKD-EPI). RESULTS: Using the Bland Altman graph, the most dispersed results were obtained with the eGFR using CCr in 24-hour urine and CKD-EPI. By means of Passing and Bablok, MDRD-4 and MDRD-6 showed the highest approximation to the reference method proposed to be substituted, whereas CCr showed a high dispersion. CONCLUSION: The eGFR using MDRD-4 and MDRD-6 formulas revealed the best adjustment to the measure by 51Cr-EDTA. This might represent the best option if a direct eGFR measure is not available.

Incidence of -93 MLH1 promoter polymorphism in familial and sporadic colorectal cancer.

AIM: The MLH1 promoter contains a common single nucleotide polymorphism (-93 guanine > adenine) located in an essential region for maximum transcriptional activity. This has been associated with an increased risk of microsatellite instability (MSI) colorectal cancer. The aim of the study was to compare the distribution of MLH1 -93G>A genotypes between patients with familial colon cancer, sporadic colon cancer and healthy subjects. METHOD: We genotyped 200 familial colon samples, 183 cases of sporadic colon cancer and 236 control subjects. MSI was analysed. RESULTS: The GA genotype was under-represented in patients with familial colon cancer, whereas the AA genotype was over-represented in cases of sporadic colon cancer. A greater frequency of the MLH1 GA genotype was found in the cancer cases with MLH1 focal immunohistochemistry (IHC) for anti-MLH1 antibody. When we compared genotype distribution in the familial colorectal cancer cases with and without MSI, we failed to detect any correlation, although the GA genotype is more frequent in cases with MSI. CONCLUSION: There is a relationship between the MLH1 -93G>A polymorphism in the homozygous state and the risk of sporadic colorectal cancer. The variant MLH1 -93G>A appears to be related to cases with focal IHC activity more than to complete absence of the MLH1 protein in the tumour tissue.

Frequency of infection by Neospora caninum in wild rodents associated with dairy farms in Aguascalientes, Mexico.

The purpose of this study was to detect the presence of Neospora caninum in tissues from wild rodents associated with dairy farms in Aguascalientes, Mexico. Individuals from Mus musculus, Rattus novergicus and Spermophilus variegatus were caught in dairy farms with history of positive status to N. caninum. A total of 33 rodents were caught from which samples were taken of brain, spinal cord, liver and heart and were tested with nested PCR and Immunohistochemistry (IHC). Results obtained with PCR showed that M. musculus had 77% (10/13) positive samples to N. caninum, S. variegatus had 71% (10/14) and R. novergicus had 50% (3/6). The results obtained with IHC showed that 15% (2/13) of M. musculus individuals were positive, while 43% (6/14) of S. variegatus and 33% (2/6) R. novergicus were also positive. This is the first report of the presence of N. caninum in S. variegatus.

A rapid reflectance-difference spectrometer for real-time semiconductor growth monitoring with sub-second time resolution.

We report on a rapid, 32-channel reflectance-difference (RD) spectrometer with sub-second spectra acquisition times and ΔR/R sensitivity in the upper 10(-4) range. The spectrometer is based on a 50 kHz photo-elastic modulator for light polarization modulation and on a lock-in amplifier for signal harmonic analysis. Multichannel operation is allowed by multiplexing the 32 outputs of the spectrometer into the input of the lock-in amplifier. The spectrometer spans a wavelength range of 230 nm that can be tuned to cover E(1) and E(1) + Δ(1) transitions for a number of III-V semiconductors at epitaxial growth temperatures, including GaAs, InAs, AlAs, and their alloys. We present two examples of real-time measurements to demonstrate the performance of the RD spectrometer, namely, the evolution of the RD spectrum of GaAs (001) annealed at 500 °C and the time-dependent RD spectrum during the first stages of the epitaxial growth of In(0.3)Ga(0.7)As on GaAs (001) substrates.

T-cell responses and in vivo cytotoxicity in the target organ and the regional lymphoid tissue during airborne infection with the virulent Mycobacterium tuberculosis MT103 and its lipid mutant fadD26.

To ascertain the in vivo role of mycobacterial lipids phthiocerol dimycocerosates (PDIM) in experimental murine tuberculosis (Tb), airways infection was used to compare the parental virulent clinical isolate MT103 with its mutant fadD26, lacking PDIM. Lungs were assessed as the Tb-target organ and mediastinal lymph nodes as the corresponding lymphoid tissue, in order to quantify: the major T-cell subsets (CD4+/CD8+/gammadelta+) and their activation kinetics, bacillary burden, and in vivo cytotoxicity against inoculated target cells loaded with mycobacterial Ags. After 4 weeks, infection augmented total and activated CD4+ and CD8+ T cells in lungs and nodes mainly with MT103, while gammadelta+ T cells increased earlier in nodes. MT103 bacillary burden was bigger and appeared earlier than the mutant fadD26, especially in the lung than in mediastinal nodes. At day 14 of MT103 infection, there was no cytotoxicity in lungs and nodes; while with fadD26 there was some in the nodes. At day 21 of MT103 infection, important cytotoxicity was detected only in lungs; while with fadD26 both tissues showed important activity. Interestingly, unlike the infection with fadD26, cytotoxicity under MT103 fell considerably in the target organ (lung) from days 21 to 60, the advanced phase. Although upon airways infection both mycobacteria behaved similarly regarding T cell (CD4/CD8/gammadelta) stimulation kinetics; they differed in the magnitude of these responses, in the bacterial load within tissues, and to trigger in vivo cytotoxicity in lungs and regional lymph nodes. This highlights the relevance of certain mycobacterial lipids to modify crucial effector branches of immunity.

Influence of porosity on Rayleigh-Taylor instabilities in reaction-diffusion systems.

We analyze the effect of porosity in a porous medium on hydrodynamic instabilities in reaction-diffusion fronts. We use an experimental device to create an effective two-dimensional porous medium which is vertically orientated. In this system the molecular diffusion coefficients and the acid autocatalysis of the chlorite-tetrathionate reaction satisfy the appropriate conditions to produce a chemical front that advances through the cell leading to the products overlaying the reactants. The reactants have a lower density than the products and therefore a buoyantly unstable front develops. To evaluate the influence of the porosity on the formation and propagation of such instabilities, media with different porosities were used in the experiments. The amplitude of the instability is found to reduce as the porosity of the medium is decreased. For sufficiently small porosity, the instability can almost disappear leading to a planar front.

Pharmaceutical companies could serve their own interests by supporting research on the efficacy of psychotherapy on premature ejaculation.

For many men, the treatment of sexual dysfunctions such as premature ejaculation may well be most effective when pharmacotherapy is combined with psychotherapy. Yet the essential elements of psychotherapy that might best be combined with pharmacological-based therapy are currently unknown. Support for evidence-based studies that identify key components of psychotherapy that might improve positive long-term outcomes, including patient satisfaction, are needed. Pharmaceutical companies having a vested interest in achieving both treatment adherence and improved patient outcomes could benefit from such information.

[Intracranial and intramedullary peripheral nerve sheath tumours. Case reports from 20 autopsies]. / Tumores de vaina de nervio periférico intracraneales e intrarraquídeos. Informe de 20 casos de autopsia.

INTRODUCTION: Tumors arising from the sheath of peripheral nerves, both intracranial and intraspinal, are uncommon and are sometimes of difficult clinical diagnosis, especially when they occur in unusual sites. Schwannomas, neurofibromas and perineuromas are depicted in this descending order of frequency. Most are sporadic and some can be part of hereditary syndromes. Histological malignancy of this neoplasm is rare. MATERIALS AND METHODS: The clinical and pathological findings of 20 autopsy cases of intracranial and intraspinal peripheral nerve tumors are analyzed. The average age at presentation was 35 years and the male/female ratio was 1:1. RESULTS: 19 were schwannomas, 13 of the 8th cranial nerve (two associated with neurofibromatosis type 2), two originated in the trigeminal and one in the 12th nerves. Three were intraspinal, one of this underwent malignant changes and was part of neurofibromatosis type 1 (NF-1), another was an intraspinal lumbar mass with schwannomatosis and the third was a case of multiple intraspinal neurofibromas as a part of NF-1. 14 cases were surgically treated and the causes of death were ischemic lesions due to the large size of the tumors. The correct clinical diagnosis was made in 14 patients. In 11 instances there was corroboration by biopsy. Three were misdiagnosed and three were autopsy findings. CONCLUSIONS: In this series more cases were sporadic. No sex predominance was encountered. The importance of early detection on intracranial and intraspinal peripheral tumors is paramount, since the large size of these histologically benign neoplasms makes them biologically malignant.

[Facial paralysis in infancy. Clinical, diagnostic and therapeutic aspects]. / Parálisis facial en la infancia. Aspectos clínicos, diagnósticos y terapéuticos.

We present seven cases of facial paralysis in newborn and infants from a series of 88 patients (pediatrics and non pediatrics) seen in a fourteen months period (October 1987 to December 1988). Current approaches to diagnosis and treatment, including pharmacological treatment with steroids and surgical treatment are described. All patients we present in this paper recovered a good facial activity and no secondary effects were found during treatment.

[Prevalence of adenomatous and hyperplastic polyps of the colon in the population of the General Hospital of Mexico. An autopsy study]. / Prevalencia de pólipos adenomatosos e hiperplásicos del colon en la población del Hospital General de México. Un estudio de autopsias.

A prospective survey of 450 autopsies was conducted to determine the prevalence of colorectal dysplastic polyps in the population of the General Hospital of Mexico City. The colon and rectum were removed and examined for the presence of polypoid lesions; their size, location, and appearance were described. All of the lesions were examined and classified according to their microscopic diagnosis. Results revealed a single polypoid lesion in nine cases; four were classified as regenerative or inflammatory and five as dysplastic. Four of the latter were in females and one in a male; their mean age was 64 years. Macroscopically four were pedunculated and one sessil; all measured less than 0.6 cm; two were located in the transverse colon and three in the left colon. No hyperplastic polyps were found. After standardization for age, comparison with similar studies performed in other countries showed an extremely low prevalence rate for dysplastic colorectal polyps (2.7%) in our patient population, similar to one reported in Iran and higher than that found in the African Bantus, but it is one of the lowest when compared with European and US series.