Hemoglobin Levels in Peruvian Patients with Chronic Kidney Disease at Different Altitudes.

Hurtado-Aréstegui, Abdías, Karina Rosales-Mendoza, Yanissa Venegas-Justiniano, José Gonzales-Polar, Rina Barreto-Jara, and Alaciel Melissa Palacios-Guillén. Hemoglobin levels in Peruvian patients with chronic kidney disease at different altitudes. High Alt Med Biol. 24:209-213, 2023. Background: Decreased hemoglobin is a manifestation of chronic kidney disease (CKD), and people who reside at high altitude adapt to hypoxia by increasing their hemoglobin. The study's objective was to determine the influence of altitude and the associated factors on the hemoglobin levels of patients with CKD who were not on dialysis (ND). Methods: This exploratory and cross-sectional study was carried out in three Peruvian cities, located at different altitudes: (1) "sea level" (161 m), (2) "moderate altitude" (2,335 m), and "high altitude" (3,399 m). The study included female and male individuals between 20 and 90 years old, with CKD stage 3a, through stage 5. Results: Of the 256 volunteers evaluated, 92 lived at sea level, 82 at moderate altitude, and 82 at high altitude. The three groups were similar in age, number of volunteers in each CKD stage, systolic blood pressure, and diastolic blood pressure. Hemoglobin levels were statistically different according to gender (p = 0.024), CKD stage, and altitude (p < 0.001). High-altitude dwellers had higher hemoglobin by 2.5 g/dl (95% confidence interval: 1.8-3.1, p < 0.001) than those living at lower altitudes (adjusted for gender, age, nutritional status, and smoking habit). For all CKD stages, the high-altitude population had higher hemoglobin levels than population at moderate altitude and at sea level. Conclusion: Subjects living at high altitude with CKD stages 3 to 5 who are yet ND have higher hemoglobin levels than those who live at moderate altitude and at sea level.

Virtual Adaptation of an International Exchange Program in Medical Education.

Medical education has drastically transformed during the COVID-19 pandemic. Measures such as adopting telemedicine visits, minimizing the number of trainees on service, discontinuing external rotations, and converting in-person to online didactics have been broadly and swiftly implemented. While these innovations have promoted greater interconnectivity amongst institutions and made continuing medical education possible, international exchange programs in medical education are still largely disrupted. In response to the changing guidelines and restrictions necessitated by the COVID-19 pandemic, the authors used Kern's six-step approach to design and implement a virtual curriculum to replace the in-person activities of the 2020-2021 Neurology Peru-Rochester exchange program (NeuroPro). Twenty-seven trainees participated in this virtual adaptation. The average daily attendance was ≥85% and the program was rated 9/10 on average in a feedback survey (63% response rate). The median percentage of correct answers during the pre-test was 64% and it increased to 79% during the post-test (P = 0.003). Virtual adaptation of international exchange programs in medical education is feasible to safely continue international collaborative efforts to promote symbiotic building of local expertise and cross-cultural exchange during the ongoing COVID-19 pandemic and beyond.

Pneumocystis primary infection in non-immunosuppressed infants in Lima, Peru.

OBJECTIVES: To provide original data on Pneumocystis primary infection in non-immunosuppressed infants from Peru. METHODS: A cross sectional study was performed. Infants less than seven months old, without any underlying medical conditions attending the "well baby" outpatient clinic at one hospital in Lima, Peru were prospectively enrolled during a 15-month period from November 2016 to February 2018. All had a nasopharyngeal aspirate (NPA) for detection of P. jirovecii DNA using a PCR assay, regardless of respiratory symptoms. P. jirovecii DNA detection was considered to represent pulmonary colonization contemporaneous with Pneumocystis primary infection. Associations between infants' clinical and demographic characteristics and results of P. jirovecii DNA detection were analyzed. RESULTS: P. jirovecii DNA was detected in 45 of 146 infants (30.8%) and detection was not associated with concurrent respiratory symptoms in 40 of 45 infants. Infants with P. jirovecii had a lower mean age when compared to infants not colonized (p <0.05). The highest frequency of P. jirovecii was observed in 2-3-month-old infants (p < 0.01) and in the cooler winter and spring seasons (p <0.01). Multivariable analysis showed that infants living in a home with ≤ 1 bedroom were more likely to be colonized; Odds Ratio =3.03 (95%CI 1.31-7.00; p = 0.01). CONCLUSION: Pneumocystis primary infection in this single site in Lima, Peru, was most frequently observed in 2-3-month-old infants, in winter and spring seasons, and with higher detection rates being associated with household conditions favoring close inter-individual contacts and potential transmission of P. jirovecii.

Saturación de oxígeno en pacientes durante hemodiálisis a diferentes altitudes

Introducción : Los pacientes en hemodiálisis pueden presentar hipoxemia durante este procedimiento, la cual puede ser mayor si la hemodiálisis se realiza en ciudades de gran altitud. Objetivos : Evaluar las variaciones de la saturación de oxígeno en pacientes en hemodiálisis a diferentes altitudes. Material y métodos : Es una serie de casos prospectivos, donde se evaluaron pacientes de un programa de hemodiálisis crónica en tres ciudades, localizadas a diferentes altitudes:101, 2 335 y3 825 metros sobre el nivel del mar, en los que se evaluó la saturación de oxígeno en posición semisentada con pulsoxímetro: antes, durante y al finalizar el procedimiento de hemodiálisis. Resultados : Se incluyeron 65 pacientes en hemodiálisis, de 3 ciudades de diferente altitud, con características similares, la saturación de oxígeno disminuyó significativamente a medida que aumentaba la altitud (97,32 ± 1,10 vs 94,75 ± 2,17 vs 84,85 ± 5,86 p=0,00), la saturación de oxígeno mostró cambios antes, durante y al final del procedimiento de hemodiálisis en las diferentes altitudes. Los niveles de ferritina fueron menores en pacientes de gran altitud comparado con los de nivel del mar y altitud moderada (131,75 [106,04 - 157,45] vs 493,38 [273,19 - 713,56] vs 550,66 [329,75-771,57] p=0,01). Los valores de hemoglobina fueron menores en los pacientes de mediana altitud (10,8 [10,12- 11,47] vs 11,32 [10,79-11,85] vs 11,84 [11,54-12,14] p=0,03). Conclusiones : En pacientes en hemodiálisis crónica la saturación de oxígeno disminuye a medida que incrementa la altitud y se encontró variaciones significativas durante el procedimiento de hemodiálisis.

Introduction : Patients undergoing hemodialysis may develop hypoxemia during the procedure, and hypoxemia may become more intense if hemodialysis is performed in a high altitude environment. Objectives: To assess variations in oxygen saturation in patients undergoing hemodialysis at different altitude levels. Material and methods : This is a prospective case series, where patients from hemodialysis programs in three cities were assessed. These places were at 101-, 2335-, and 3825- meters above sea level. Patients had their oxygen saturation measured in a semi-sitting position with a pulse oxymeter device. Measurements were taken before, during, and at the end of hemodialysis sessions. Results : Sixty-five patients undergoing hemodialysis were included. They were from three cities at different altitude above sea level. Oxygen saturation significantly decreased as long as altitude increased (97,32 ± 1,10 vs. 94,75 ± 2,17 vs. 84,85 ± 5,86 p= 0,00). Oxygen saturation showed changes before, during, and at the end of hemodialysis procedures at different altitude. Ferritin levels were lower in high altitude patients compared with those at sea level and at moderate altitude (131,75 [106,04 - 157,45] vs. 493,38 [273,19 - 713,56] vs. 550,66 [329,75-771,57] p=0,01). Hemoglobin values were lower in patients from middle altitude levels (10,8 [10,12-11,47] vs 11,32 [10,79-11,85] vs 11,84 [11,54-12,14] p=0,03). Conclusions : In patients undergoing chronic hemodialysis oxygen saturation is reduced as long as altitude increases, and significant variations were found during hemodialysis procedures.

Expression of miR-34a and miR-15b during the progression of cervical cancer in a murine model expressing the HPV16 E7 oncoprotein.

The high-risk human papillomavirus (HR-HPV) E7 oncoprotein appears to be a major determinant for cell immortalization and transformation altering critical processes such as cell proliferation, apoptosis, and immune response. This oncoprotein plays an essential role in cervical carcinogenesis, but other cofactors such as long-term use of hormonal contraceptives are necessary to modulate the risk of cervical cancer (CC). The role of HR-HPVs in the alteration of microRNA (miRNA) levels in persistent viral infections currently remains unclear. The aim of this study was to evaluate the miR-34a and miR-15b expression levels in the murine HPV16K14E7 (K14E7) transgenic model after chronic estrogen (E2) treatment and their involvement in CC. Interestingly, results showed that, although miR-34a expression is elevated by the HPVE7 oncogene, this expression was downregulated in the presence of both the E7 oncoprotein and chronic E2 in cervical carcinoma. On the other hand, miR-15b expression was upregulated along cervical carcinogenesis mainly by the effect of E2. These different changes in the expression levels of miR-34a and miR-15b along cervical carcinogenesis conduced to low apoptosis levels, high cell proliferation and finally, to cancerous cervical tissue development. In this work, we also determined the relative mRNA expression of Cyclin E2 (Ccne2), Cyclin A2 (Ccna2), and B cell lymphoma 2 (Bcl-2) (target genes of miR-34a and miR-15b); Sirtuin 1 (Sirt1), Cmyc, and Bax (miR-34a target genes); and p21/WAF1 (mir15b target gene) and the H-ras oncogene. Given the modifications in the expression levels of miR-34a and miR-15b during the development of cervical cancer, it will be useful to carry out further investigation to confirm them as molecular biomarkers of cancer.

Solventless Preparation of Thoria and Its Inclusion into SiO2 and TiO2: A Luminescence and Photocatalysis Study.

Thoria was prepared using a solid-state method from the macromolecular precursor Chitosan·Th(NO3)4 (chitosan) and PS-co-4-PVP·Th(NO3)4 (PVP). The morphology and the average size of ThO2 depend of the chitosan and PS-co-4-PVP polymer forming the precursor. Their photoluminescent properties were investigated, finding a dependence of their intensity emission maxima, with the nature of the precursor polymer. The photocatalytic activity of ThO2 toward the degradation of methylene blue was measured for the first time, finding a degradation of about 66% in 300 min. The inclusion of ThO2 into SiO2 and TiO2 was achieved by the solid-state pyrolysis of the macromolecular composites Chitosan·Th(NO3)4//MO2 and PS-co-4-PVP·Th(NO3)4//MO2, MO2 = SiO2 or TiO2. The ThO2 exhibits a homogeneous dispersion inside the silica, showing sizes of about 40 and 50 nm for the chitosan and PVP polymer precursors, respectively. The luminescent properties of the ThO2/SiO2 and ThO2/TiO2 composites were also studied, finding a decrease in intensity when introducing the SiO2 or TiO2 matrices. The photocatalytic behavior to methylene blue degradation of ThO2 and their composites ThO2/SiO2 and ThO2/TiO2 was investigated for the first time, with them in the following order: ThO2 > ThO2/TiO2 > ThO2/SiO2.

Effect of bovine lactoferrin on prevention of late-onset sepsis in infants <1500 g: a pooled analysis of individual patient data from two randomized controlled trials.

We previously conducted two randomized controlled trials with bovine lactoferrin (bLF) for the prevention of late-onset sepsis (LOS) in infants with a birth weight <2500 g (Study 1) and <2000 g (Study 2). The aim of this study was to determine the preventative effects of bLF on culture-proven or probable LOS in infants with a birth weight <1500 g from both studies, and to determine the effect of bLF in relation to intake of human milk. Both trial designs had similar inclusion and exclusion criteria, the same dose of bLF [200 mg·(kg body mass)-1·day-1], and used the same control (maltodextrin). We fitted multivariate Cox regression models to estimate the effect of bLF on the risk of development of the composite outcome, adjusting for covariates. We included 335 neonates with a mean birth weight of 1162 ± 244 g; 27.5% were <1000 g. There were 33 first episodes of LOS in the bLF treatment group and 48 in the control group (19.5% vs. 28.9%). bLF had a protective effect on the risk of development of LOS [hazard ratio (HR) = 0.64; %95 CI = 0.41-0.99; p = 0.048]; particularly among infants weighing <1000 g [HR = 0.46; %95 CI = 0.22-0.96; p = 0.039] and infants with a low intake of human milk [HR = 0.40; %95 CI = 0.19-0.84; p = 0.015]. Therefore, bLF supplementation protects infants <1500 g from LOS, particularly those infants not receiving human milk.

Is Mother's Own Milk Lactoferrin Intake Associated with Reduced Neonatal Sepsis, Necrotizing Enterocolitis, and Death?

INTRODUCTION: Lactoferrin (LF) is a protective protein present in milk with anti-infective and immune-modulating properties. OBJECTIVES: The aim of this study was to determine the association of maternal LF intake and mother's own milk intake in the first 10 days of life on the prevention of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), or death in the first 8 weeks of life in newborns with a birth weight <2,000 g. METHODS: A retrospective cohort study was conducted, with the exposure being the consumption of mother's own LF and mother's own milk in the first 10 days of life, and the outcome being LOS, NEC, or death during days 11 and 56 of life, analyzed by Cox regression. RESULTS: Two hundred and ninety-nine infants were enrolled, including 240 with human LF intake information. The average daily human LF intake over days 4-10 of life was 283 mg/kg/day (IQR 114-606 mg/kg/day). The hazard ratio (HR) of mother's own milk LF intake ≥100 mg/kg/day in days 4-10 for LOS, NEC, or death was 0.297 (95% CI 0.156-0.568, p < 0.001); the adjusted HR was 0.752 (95% CI 0.301-1.877, p = 0.541). The adjusted HR of mother's own milk cumulative intake (days 4-10) of 54-344 mL/kg (25-75 quartiles) for LOS, NEC, or death was 0.414 (95% CI 0.196-0.873, p = 0.02). Infants who developed an event (LOS, NEC, or death) had significantly less median daily human LF intake than those that did not (89 vs. 334 mg/kg/day, respectively, p < 0.0001). CONCLUSION: Consumption of higher amounts of mother's own milk in the first days of life is associated with less infection, NEC, and death. Early human milk intake should be strongly encouraged in all newborns.

Theoretical study of 3-D molecular similarity and ligand binding modes of orthologous human and rat D2 dopamine receptors.

The D(2) dopamine receptor (D(2)DR) is an important target for the treatment of some central nervous system disorders, such as Parkinson disease, schizophrenia and drug-dependence. In this work, we built 3-D models of the long form of human and rat D(2)DRs by considering data from the crystallized D3 dopamine receptor, ß2 adrenoceptor and A2a adenosine receptor as templates. Then, docking was performed with ligand and protein residue flexibility. These results were used to analyze ligand recognition and estimate binding affinity. Our results show that the predicted ligand affinity correlates with experimental data, and binding modes are very similar between the D(2)DRs of these two species.

The hexokinase gene family in the zebrafish: structure, expression, functional and phylogenetic analysis.

Hexokinase-catalyzed glucose phosphorylation is the first and crucial step for glucose utilization. Although there are reported studies on glucose metabolism in commercial species, knowledge on it is almost nil in zebrafish (Danio rerio), an important model organism for biological research. We have searched these fish hexokinase genes by BLAST analysis; determined their expression in liver, muscle, brain and heart; measured their response to fasting and glucose administration; and performed homology sequences studies to glimpse their evolutionary history. We have confirmed by RT-qPCR studies that the six DNA sequences annotated as possible hexokinases in the NCBI GenBank are transcribed. The organ distribution of the HXK genes is similar in zebrafish as in mammals, to which they are distantly related. Of these, DrGLK and DrSHXK1 are expressed in the fish liver, DrHXK1 in brain and heart, and DrHXK2 in muscle. The only gene responsive to glucose was liver DrGLK. Its expression is induced approximately 1 h after glucose intraperitoneal injection, but not after saline solution injection. The comparison of the fish sequences and the corresponding mammalian ones imply that in both taxa the main muscle and brain isoforms are fusion products of the ancestral gene, their amino halves having separated before than their carboxy ones, followed by the fusion event, whereas fish and mammalian glucokinase genes remained unduplicated.