Oxaliplatin is a chemotherapeutic agent with direct toxic action on deoxyribonucleic acid (DNA), ... more Oxaliplatin is a chemotherapeutic agent with direct toxic action on deoxyribonucleic acid (DNA), which is known to cause an arrest in its synthesis and inducing cell death. It is a crucial medication for colorectal carcinoma, and in combination with other medications has demonstrated to exhibit synergism, managing to increase patients' survival, especially when compared to monotherapy with 5-fluoracil. Neurotoxicity is its most well-known adverse effect. However, other less frequent secondary effects have been described in case reports, among them liver injury, which is usually secondary to liver sinusoid injury. Despite the wide frequency of the use of this drug, the relationship of oxaliplatin with the development of portal non-cirrhotic hypertension is largely unknown, which translates into a sub-diagnosis, representing an additional risk to patients who develop this complication. We present the case of an adult patient, who during treatment with the FOLFOX scheme for colorectal carcinoma, presents signs suggestive of portal hypertension, without other risk factors besides the administration of oxaliplatin.
The role of elevated sea temperatures in coral bleaching has been well documented. Many of the se... more The role of elevated sea temperatures in coral bleaching has been well documented. Many of the sea temperature records utilized for purposes of widespread, multi-species bleaching predictions in recent publications, have been acquired through satellite remote sensing. Satellites estimate sea temperatures at only a narrow range of depths near the surface of the ocean and may therefore not adequately represent the true temperatures endured by the world’s coral ecosystems. To better characterize sea temperature regimes that coral reef ecosystems experience, as well as better define the individual thresholds for each species that bleaches, in situ sea temperature sensors are required. Commercial sensors are expensive in large quantities, however, reducing the capacity to conduct large-scale research programs to elucidate the range of significant scales of temperature variability. At the National Oceanic and Atmospheric Administration’s (NOAA) Atlantic Oceanographic and Meteorological La...
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2016
The Large T Antigen (TAg) of polyomaviruses (PyVs) is a helicase required for viral DNA replicati... more The Large T Antigen (TAg) of polyomaviruses (PyVs) is a helicase required for viral DNA replication and an oncoprotein that stimulates quiescent cells to reenter a proliferative state conducive to viral DNA synthesis. In doing so, TAg engages in multiple protein-protein interactions with host DNA replication and cell-cycle control machineries. To identify which viral-host interaction might be susceptible to competition by a peptidic inhibitor, we scanned the TAg protein with 50-60 amino acid long overlapping peptides for functional dominant-negative inhibitors in our cell-based assay of SV40 DNA replication. This method identified a potent inhibitory peptide derived from the first exon of TAg which bears high sequence homology with the J-domain of the Hsp40/DNAJ co-chaperone family, and is required for viral DNA replication. Studies have found that the J-domain interacts with Hsc70 and stimulates its ATPase/chaperone activity, to release E2F from pRb-containing complexes bound to TAg to promote viral DNA replication and transformation. Characterization of our J-domain inhibitory peptide (aa 2-64) confirmed that it interacts with Hsc70. Mutagenesis of the HPD motif conserved in all known DnaJ homologues, abolished the interaction of the peptide with Hsc70 and its ability to inhibit SV40 DNA replication. Notably, the overexpression of this J-domain peptide could also inhibit viral DNA replication for the clinically relevant human PyVs JCV, BKV and MCV, whose reactivation in immunocompromised patients is associated with the development of progressive multifocal leukencephalopathy, BK-induced nephropathy, and Merkel Cell Carcinoma respectively. Collectively, these results suggest that the J-domain peptide inhibits viral DNA replication by competing with full length TAg for Hsc70 binding. As such, this peptide represents a promising tool to study the function of Hsc70 in PyV DNA replication and to develop therapies for the treatment of PyV-associated diseases including Merkel Cell Carcinoma caused by MCPyV.
Study Objective: To compare spinal anesthesia and combined sciatic-femoral nerve block for outpat... more Study Objective: To compare spinal anesthesia and combined sciatic-femoral nerve block for outpatient knee arthroscopy. Design: Prospective, randomized, controlled study. Setting: Postoperative recovery area at a university-affiliated medical center. Patients: 50 ASA physical status I and II adult outpatients undergoing arthroscopic knee surgery. Interventions: Study subjects were equally divided (n = 25 each) into spinal and sciatic-femoral groups. Spinal group patients received spinal anesthesia with 7.5 mg of 0.5% hyperbaric bupivacaine. Sciaticfemoral group patients received combined sciatic-femoral nerve blocks using a mixture of 20 mL of lidocaine 2% plus 20 mL of bupivacaine 0.5%. Measurements: Times including that from arrival in the operating room to readiness for surgery, duration of surgery, recovery time, and patient satisfaction were recorded. Analgesia and occurrence of adverse events also were recorded. Main Results: No significant differences between the two groups were found for any of the study measurements of recovery. After discharge, postoperative pain differed significantly between groups only at 6 hours (P b 0.002). Patient satisfaction was high with both techniques. Conclusions: Combined sciatic-femoral nerve block for outpatient arthroscopic knee surgery offers satisfactory anesthesia, with a clinical profile similar to that of low-dose spinal anesthesia. Sciatic-femoral nerve blocks are associated with significantly lower pain scores during the first 6 postoperative hours.
The cities of Rivera and Santana do Livramento are located on the outcropping area of the sandsto... more The cities of Rivera and Santana do Livramento are located on the outcropping area of the sandstone Guarani Aquifer on the Brazil-Uruguay border, where the aquifer is being increasingly exploited. Therefore, recharge estimates are needed to address sustainability. First, a conceptual model of the area was developed. A multilayer, heterogeneous and anisotropic groundwaterflow model was built to validate the conceptual model and to estimate recharge. A field campaign was conducted to collect water samples and monitor water levels used for model calibration. Field data revealed that there exists vertical gradients between confining basalts and underlying sandstones, suggesting basalts could indirectly recharge sandstone in fractured areas. Simulated downward flow between them was a small amount within the global water budget. Calibrated recharge rates over basalts and over outcropping sandstones were 1.3 and 8.1% of mean annual precipitation, respectively. A big portion of sandstone recharge would be drained by streams. The application of a water balance yielded a recharge of 8.5% of average annual precipitation. The numerical model and the water balance yielded similar recharge values consistent with determinations from previous authors in the area and other regions of the aquifer, providing an upper bound for recharge in this transboundary aquifer.
Background: Thyroid dysfunction is associated with negative neonatal and obstetric outcomes. Larg... more Background: Thyroid dysfunction is associated with negative neonatal and obstetric outcomes. Large differences in thyroid function reference intervals exist across different populations. These differences can be explained by population-specific factors, such as iodine status. Many countries in Latin America report iodine sufficiency, but relatively few countries have published up-to-date data on iodine levels and thyroid function in the overall population, and especially in pregnant women. We evaluated the iodine status of pregnant women in Chile and determined thyroid hormone reference ranges in this population. Methods: This was a prospective observational study of healthy Chilean women at their first prenatal visit before week 14. Thyroidstimulating hormone (TSH), total thyroxine (T4), free T4, antithyroid peroxidase antibody (TPOAb), and iodine levels from spot urine samples were measured. Iodine status and the reference ranges for TSH were calculated. Results: A total of 1,022 pregnant women in the first trimester were selected. Urinary iodine levels were measured in 302 randomlyselected women. The median urinary iodine concentration was 173.45 μg/L (interquartile range, 108.11 to 249.35).The reference ranges of TSH were calculated in 670 patients selected according to the National Academy of Clinical Biochemistry guidelines. The median TSH level was 1.88 μIU/mL (2.5th percentile: 0.13 to 97.5th percentile: 5.37). Using the reference range in the 1,022 women, the prevalence of clinical hypothyroidism was 1.76%, and that of subclinical hypothyroidism was 3.92%. TPOAb positivity was more common in women with TSH levels above 3.5 μIU/mL. Conclusion: We found adequate iodine intake and a right-shifted distribution of serum TSH levels in pregnant women in Chile. The prevalence of hypothyroidism in our sample of pregnant women was higher than has been described in the literature.
Oxaliplatin is a chemotherapeutic agent with direct toxic action on deoxyribonucleic acid (DNA), ... more Oxaliplatin is a chemotherapeutic agent with direct toxic action on deoxyribonucleic acid (DNA), which is known to cause an arrest in its synthesis and inducing cell death. It is a crucial medication for colorectal carcinoma, and in combination with other medications has demonstrated to exhibit synergism, managing to increase patients' survival, especially when compared to monotherapy with 5-fluoracil. Neurotoxicity is its most well-known adverse effect. However, other less frequent secondary effects have been described in case reports, among them liver injury, which is usually secondary to liver sinusoid injury. Despite the wide frequency of the use of this drug, the relationship of oxaliplatin with the development of portal non-cirrhotic hypertension is largely unknown, which translates into a sub-diagnosis, representing an additional risk to patients who develop this complication. We present the case of an adult patient, who during treatment with the FOLFOX scheme for colorectal carcinoma, presents signs suggestive of portal hypertension, without other risk factors besides the administration of oxaliplatin.
The role of elevated sea temperatures in coral bleaching has been well documented. Many of the se... more The role of elevated sea temperatures in coral bleaching has been well documented. Many of the sea temperature records utilized for purposes of widespread, multi-species bleaching predictions in recent publications, have been acquired through satellite remote sensing. Satellites estimate sea temperatures at only a narrow range of depths near the surface of the ocean and may therefore not adequately represent the true temperatures endured by the world’s coral ecosystems. To better characterize sea temperature regimes that coral reef ecosystems experience, as well as better define the individual thresholds for each species that bleaches, in situ sea temperature sensors are required. Commercial sensors are expensive in large quantities, however, reducing the capacity to conduct large-scale research programs to elucidate the range of significant scales of temperature variability. At the National Oceanic and Atmospheric Administration’s (NOAA) Atlantic Oceanographic and Meteorological La...
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2016
The Large T Antigen (TAg) of polyomaviruses (PyVs) is a helicase required for viral DNA replicati... more The Large T Antigen (TAg) of polyomaviruses (PyVs) is a helicase required for viral DNA replication and an oncoprotein that stimulates quiescent cells to reenter a proliferative state conducive to viral DNA synthesis. In doing so, TAg engages in multiple protein-protein interactions with host DNA replication and cell-cycle control machineries. To identify which viral-host interaction might be susceptible to competition by a peptidic inhibitor, we scanned the TAg protein with 50-60 amino acid long overlapping peptides for functional dominant-negative inhibitors in our cell-based assay of SV40 DNA replication. This method identified a potent inhibitory peptide derived from the first exon of TAg which bears high sequence homology with the J-domain of the Hsp40/DNAJ co-chaperone family, and is required for viral DNA replication. Studies have found that the J-domain interacts with Hsc70 and stimulates its ATPase/chaperone activity, to release E2F from pRb-containing complexes bound to TAg to promote viral DNA replication and transformation. Characterization of our J-domain inhibitory peptide (aa 2-64) confirmed that it interacts with Hsc70. Mutagenesis of the HPD motif conserved in all known DnaJ homologues, abolished the interaction of the peptide with Hsc70 and its ability to inhibit SV40 DNA replication. Notably, the overexpression of this J-domain peptide could also inhibit viral DNA replication for the clinically relevant human PyVs JCV, BKV and MCV, whose reactivation in immunocompromised patients is associated with the development of progressive multifocal leukencephalopathy, BK-induced nephropathy, and Merkel Cell Carcinoma respectively. Collectively, these results suggest that the J-domain peptide inhibits viral DNA replication by competing with full length TAg for Hsc70 binding. As such, this peptide represents a promising tool to study the function of Hsc70 in PyV DNA replication and to develop therapies for the treatment of PyV-associated diseases including Merkel Cell Carcinoma caused by MCPyV.
Study Objective: To compare spinal anesthesia and combined sciatic-femoral nerve block for outpat... more Study Objective: To compare spinal anesthesia and combined sciatic-femoral nerve block for outpatient knee arthroscopy. Design: Prospective, randomized, controlled study. Setting: Postoperative recovery area at a university-affiliated medical center. Patients: 50 ASA physical status I and II adult outpatients undergoing arthroscopic knee surgery. Interventions: Study subjects were equally divided (n = 25 each) into spinal and sciatic-femoral groups. Spinal group patients received spinal anesthesia with 7.5 mg of 0.5% hyperbaric bupivacaine. Sciaticfemoral group patients received combined sciatic-femoral nerve blocks using a mixture of 20 mL of lidocaine 2% plus 20 mL of bupivacaine 0.5%. Measurements: Times including that from arrival in the operating room to readiness for surgery, duration of surgery, recovery time, and patient satisfaction were recorded. Analgesia and occurrence of adverse events also were recorded. Main Results: No significant differences between the two groups were found for any of the study measurements of recovery. After discharge, postoperative pain differed significantly between groups only at 6 hours (P b 0.002). Patient satisfaction was high with both techniques. Conclusions: Combined sciatic-femoral nerve block for outpatient arthroscopic knee surgery offers satisfactory anesthesia, with a clinical profile similar to that of low-dose spinal anesthesia. Sciatic-femoral nerve blocks are associated with significantly lower pain scores during the first 6 postoperative hours.
The cities of Rivera and Santana do Livramento are located on the outcropping area of the sandsto... more The cities of Rivera and Santana do Livramento are located on the outcropping area of the sandstone Guarani Aquifer on the Brazil-Uruguay border, where the aquifer is being increasingly exploited. Therefore, recharge estimates are needed to address sustainability. First, a conceptual model of the area was developed. A multilayer, heterogeneous and anisotropic groundwaterflow model was built to validate the conceptual model and to estimate recharge. A field campaign was conducted to collect water samples and monitor water levels used for model calibration. Field data revealed that there exists vertical gradients between confining basalts and underlying sandstones, suggesting basalts could indirectly recharge sandstone in fractured areas. Simulated downward flow between them was a small amount within the global water budget. Calibrated recharge rates over basalts and over outcropping sandstones were 1.3 and 8.1% of mean annual precipitation, respectively. A big portion of sandstone recharge would be drained by streams. The application of a water balance yielded a recharge of 8.5% of average annual precipitation. The numerical model and the water balance yielded similar recharge values consistent with determinations from previous authors in the area and other regions of the aquifer, providing an upper bound for recharge in this transboundary aquifer.
Background: Thyroid dysfunction is associated with negative neonatal and obstetric outcomes. Larg... more Background: Thyroid dysfunction is associated with negative neonatal and obstetric outcomes. Large differences in thyroid function reference intervals exist across different populations. These differences can be explained by population-specific factors, such as iodine status. Many countries in Latin America report iodine sufficiency, but relatively few countries have published up-to-date data on iodine levels and thyroid function in the overall population, and especially in pregnant women. We evaluated the iodine status of pregnant women in Chile and determined thyroid hormone reference ranges in this population. Methods: This was a prospective observational study of healthy Chilean women at their first prenatal visit before week 14. Thyroidstimulating hormone (TSH), total thyroxine (T4), free T4, antithyroid peroxidase antibody (TPOAb), and iodine levels from spot urine samples were measured. Iodine status and the reference ranges for TSH were calculated. Results: A total of 1,022 pregnant women in the first trimester were selected. Urinary iodine levels were measured in 302 randomlyselected women. The median urinary iodine concentration was 173.45 μg/L (interquartile range, 108.11 to 249.35).The reference ranges of TSH were calculated in 670 patients selected according to the National Academy of Clinical Biochemistry guidelines. The median TSH level was 1.88 μIU/mL (2.5th percentile: 0.13 to 97.5th percentile: 5.37). Using the reference range in the 1,022 women, the prevalence of clinical hypothyroidism was 1.76%, and that of subclinical hypothyroidism was 3.92%. TPOAb positivity was more common in women with TSH levels above 3.5 μIU/mL. Conclusion: We found adequate iodine intake and a right-shifted distribution of serum TSH levels in pregnant women in Chile. The prevalence of hypothyroidism in our sample of pregnant women was higher than has been described in the literature.
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Papers by Andrea Gomez