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1.
Nature ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867050

ABSTRACT

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species1. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe1,2. To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax and P. malariae from 16 countries spanning around 5,500 years of human history. We identified P. vivax and P. falciparum across geographically disparate regions of Eurasia from as early as the fourth and first millennia BCE, respectively; for P. vivax, this evidence pre-dates textual references by several millennia3. Genomic analysis supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between now-eliminated European and peri-contact South American strains indicate that European colonizers were the source of American P. vivax, whereas the trans-Atlantic slave trade probably introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the dissemination of malaria, laying the biomolecular foundation for future palaeo-epidemiological research into the impact of Plasmodium parasites on human history. Finally, our unexpected discovery of P. falciparum in the high-altitude Himalayas provides a rare case study in which individual mobility can be inferred from infection status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago.

2.
J Clin Med ; 13(10)2024 May 09.
Article in English | MEDLINE | ID: mdl-38792322

ABSTRACT

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

3.
Front Public Health ; 11: 1240392, 2023.
Article in English | MEDLINE | ID: mdl-38074750

ABSTRACT

Worldwide, Urinary Tract Infections (UTIs) are an important health problem with many cases reported annually, women being the most affected. UTIs are relevant because they can become a recurrent condition, associated with different factors that contribute to the chronicity of the disease (cUTI). cUTI can be classified as persistent (peUTI) when the causative agent is the same each time the infection occurs or as reinfection (reUTI) when the associated microorganism is different. The purpose of this work was to characterize Escherichia coli isolates obtained in two prospective studies of patients with cUTI, to define which of them corresponded to peUTI and which to reUTI. A total of 394 isolates of E. coli were analyzed by agglutination with specific sera, antimicrobial susceptibility by diffusion disc test, and the phylogroups and presence of genes associated with virulence by PCR assays. Additionally, in some characterized strains adherence, invasiveness, and biofilm formation were analyzed by in vitro assays. The results showed that the peUTI strains belonged mainly to the classical UPEC serogroups (O25, O75, O6), were included in the B2 phylogroup, carried a great number of virulence genes, and were adherent, invasive, and biofilm-forming. Meanwhile, reUTI strains showed great diversity of serogroups, belonged mainly in the A phylogroup, and carried fewer virulence genes. Both peUTI and reUTI strains showed extensively drug-resistant (XDR) and multidrug-resistant (MDR) profiles in the antimicrobial susceptibility test. In conclusion, it appears that peUTIs are caused principally by classical UPEC strains, while reUTIs are caused by strains that appear to be a part of the common E. coli intestinal biota. Moreover, although both peUTI and reUTI strains presented different serotypes and phylogroups, their antimicrobial resistance profile (XDR and MDR) was similar, confirming the importance of regulating prophylactic treatments and seeking alternatives for the treatment and control of cUTI. Finally, it was possible to establish the features of the E. coli strains responsible for peUTI and reUTI which could be helpful to develop a fast diagnostic methodology.


Subject(s)
Anti-Infective Agents , Escherichia coli Infections , Urinary Tract Infections , Humans , Female , Escherichia coli/genetics , Follow-Up Studies , Escherichia coli Infections/diagnosis , Prospective Studies , Virulence Factors/analysis , Virulence Factors/genetics , Urinary Tract Infections/diagnosis
5.
Molecules ; 28(14)2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37513235

ABSTRACT

Highly neurotoxic A1-reactive astrocytes have been associated with several human neurodegenerative diseases. Complement protein C3 expression is strongly upregulated in A1 astrocytes, and this protein has been shown to be a specific biomarker of these astrocytes. Several cytokines released in neurodegenerative diseases have been shown to upregulate the production of amyloid ß protein precursor (APP) and neurotoxic amyloid ß (Aß) peptides in reactive astrocytes. Also, aberrant Ca2+ signals have been proposed as a hallmark of astrocyte functional remodeling in Alzheimer's disease mouse models. In this work, we induced the generation of A1-like reactive astrocytes after the co-treatment of U251 human astroglioma cells with a cocktail of the cytokines TNF-α, IL1-α and C1q. These A1-like astrocytes show increased production of APP and Aß peptides compared to untreated U251 cells. Additionally, A1-like astrocytes show a (75 ± 10)% decrease in the Ca2+ stored in the endoplasmic reticulum (ER), (85 ± 10)% attenuation of Ca2+ entry after complete Ca2+ depletion of the ER, and three-fold upregulation of plasma membrane calcium pump expression, with respect to non-treated Control astrocytes. These altered intracellular Ca2+ dynamics allow A1-like astrocytes to efficiently counterbalance the enhanced release of Ca2+ from the ER, preventing a rise in the resting cytosolic Ca2+ concentration.


Subject(s)
Calcium , Neurodegenerative Diseases , Mice , Animals , Humans , Calcium/metabolism , Up-Regulation , Astrocytes/metabolism , Amyloid beta-Peptides/metabolism , Calcium Signaling , Amyloid beta-Protein Precursor/genetics , Neurodegenerative Diseases/metabolism , Cell Membrane/metabolism
6.
Retina ; 43(12): 2144-2147, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-35594575

ABSTRACT

PURPOSE: Vitrectomy for severe tractional retinal detachments is a high-risk procedure given the surgical complexity and potential for postoperative complications. The risk is compounded when operating on monocular patients. We developed a novel technique using hyaloidal removal and minimal relaxing membranectomies for tractional retinal detachments with an opacified hyaloid over the fovea in monocular, diabetic patients and evaluated complications and outcomes. METHODS: The technique was performed in nine monocular, diabetic patients with decreased visual acuity from opaque hyaloid with centripetal tractional retinal detachments. Outcomes included postoperative best-corrected visual acuity, retinal reattachment rate, redetachments, and complications. RESULTS: Average age was 58 years (range 43-74) and the average follow-up time was 43.6 months (range 36-64). Preoperative best-corrected visual acuity ranged from 1.0 to 2.3 logMAR (20/200 - Hand Motion) with a mean of 1.39 logMAR (20/500). Postoperative best-corrected visual acuity at last follow-up ranged from 0.2 to 1.0 logMAR (20/30-20/200) with a mean of 0.49 logMAR (20/60) ( P < 0.001). All eyes had attached posterior poles at last follow-up. Complications were observed in two eyes and included nonclearing hemorrhage and capsular opacity. CONCLUSION: Vitrectomy with minimal, relaxing membranectomies is an option for monocular patients in whom intervention is needed, but are at high risk for complications.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Retinal Detachment , Humans , Child, Preschool , Child , Retinal Detachment/etiology , Retinal Detachment/surgery , Diabetic Retinopathy/complications , Diabetic Retinopathy/surgery , Retina , Vitrectomy/methods , Postoperative Complications/surgery , Retrospective Studies , Treatment Outcome
7.
Neuroscience ; 518: 112-118, 2023 05 10.
Article in English | MEDLINE | ID: mdl-35469971

ABSTRACT

Disruption of calcium (Ca2+) homeostasis is emerging as a prevalent feature of aging and aging-associated neurodegenerative diseases, including Alzheimer's disease (AD), the most common type of tauopathy. This disease is characterized by the combined presence of extracellular neuritic plaques composed by amyloid ß-peptides (Aß) and neurofibrillary tangles of tau. The association of calcium dyshomeostasis with Aß has been extensively studied, however its link with tau has been less investigated. Thus, this review will concentrate on the functional link between tau and the plasma membrane Ca2+ pump (PMCA) and other membrane proteins involved in the regulation of intracellular calcium and/or its association with neurodegeneration.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Humans , Amyloid beta-Peptides/metabolism , Calcium/metabolism , Adenosine Triphosphatases/metabolism , tau Proteins/metabolism , Plasma Membrane Calcium-Transporting ATPases/metabolism , Alzheimer Disease/metabolism , Cell Membrane/metabolism , Neurofibrillary Tangles/metabolism
8.
J Inorg Biochem ; 236: 111952, 2022 11.
Article in English | MEDLINE | ID: mdl-36049257

ABSTRACT

Plasma membrane calcium ATPases (PMCA) and sarco(endo) reticulum calcium ATPases (SERCA) are key proteins in the maintenance of calcium homeostasis. Herein, we compare for the first time the inhibition of SERCA and PMCA calcium pumps by several polyoxotungstates (POTs), namely by Wells-Dawson phosphotungstate anions [P2W18O62]6- (intact, {P2W18}), [P2W17O61]10- (monolacunary, {P2W17}), [P2W15O56]12- (trilacunary, {P2W15}), [H2P2W12O48]12- (hexalacunary, {P2W12}), [H3P2W15V3O62]6- (trivanadium-substituted, {P2W15V3}) and by Preyssler-type anion [NaP5W30O110]14- ({P5W30}). The speciation in the solutions of tested POTs was investigated by 31P and 51V NMR spectroscopy. The tested POTs inhibited SERCA Ca2+-ATPase activity, whereby the Preyssler POT showed the strongest effect, with an IC50 value of 0.37 µM. For {P2W17} and {P2W15V3} higher IC50 values were determined: 0.72 and 0.95 µM, respectively. The studied POTs showed to be more potent inhibitors of PMCA Ca2+-ATPase activity, with lower IC50 values for {P2W17}, {P5W30} and {P2W15V3}.


Subject(s)
Calcium , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Calcium/chemistry , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
9.
J Clin Med ; 11(18)2022 Sep 14.
Article in English | MEDLINE | ID: mdl-36143049

ABSTRACT

The purpose of this study was to evaluate the long-term, real-world outcomes of pars plana vitrectomy (PPV) for complications of proliferative diabetic retinopathy. A retrospective review involving 64 patients with proliferative diabetic retinopathy that underwent PPV in their worse-seeing eye were followed for a minimum of 8 years. The fellow eye underwent conventional treatment. Patients were divided into two groups by age: patients younger than 50 years of age and patients older than 50. In the younger than 50 group, 89% of vitrectomized eyes had improved visual acuity (VA) while 3.6% had decreased VA. A total of 14% of vitrectomized eyes required additional laser and 11% required reoperations. In the conventional treatment eyes, 25% had improved VA while 68% had decreased VA (p < 0.05). A total of 72% required additional laser and 60% required PPV. In the older than 50 group, 86% of vitrectomized eyes had VA improvement and 3% had decreased VA. A total of 8% required laser and 8% required reoperations. In the conventional treatment eyes, 30% improved VA and 48% had decreased VA (p < 0.05). Additional procedures required included laser in 70% and PPV in 17%. In both age groups, eyes that underwent PPV had better final visual outcomes than eyes that received conventional treatment for PDR.

10.
Ophthalmol Retina ; 6(7): 595-606, 2022 07.
Article in English | MEDLINE | ID: mdl-35304304

ABSTRACT

PURPOSE: To determine the practice pattern for treating giant retinal tear (GRT) related detachments, and their anatomic and visual outcomes with pars plana vitrectomy (PPV) with or without scleral buckling (SB). DESIGN: Retrospective cohort study. SUBJECTS: Eyes with GRT detachments repaired from 2008 to 2020 with at least 6 months of follow-up from 7 institutions in North and South America, Europe, and Asia. METHODS: Eyes repaired using PPV versus PPV/SB were compared. MAIN OUTCOME MEASURES: Anatomic and functional outcomes. RESULTS: A comparable number of eyes underwent PPV (n = 101) and PPV/SB (n = 99). Except for history of developmental abnormalities, prior intraocular surgery, and lens status, no differences in baseline demographics, ocular characteristics, or intraoperative surgical adjuncts were observed. The overall single surgery anatomic success (SSAS) at 6 months and 1 year were similar between the groups (82.2% and 77.2% of PPV, and 87.9% and 85.7% of PPV/SB). When stratified by age, the 1-year SSAS rate was higher for PPV/SB (88.5%) than PPV (56.3%) (P = 0.03) for children <18 years. For both children and adults, the mean best-corrected visual acuity (BCVA) at baseline did not differ between the PPV and PPV/SB groups. However, for children, mean BCVA at 1 year was better in the PPV/SB than PPV groups (P = 0.001) while for adults, no difference was found between the 2 groups. The mean time to the first redetachment was 7.9 months in the PPV group and 5.5 months in the PPV/SB group (P = 0.8). Proliferative vitreoretinopathy was the most common cause for redetachment (70.4% of PPV and 93.8% of PPV/SB in redetached eyes; P = 0.1). Postoperative complications were also similar between the 2 groups, including ocular hypertension, epiretinal membrane, and cataract formation. CONCLUSIONS: PPV and PPV/SB are equally popular among surgeons globally for managing GRT detachments and have comparable anatomic and visual outcomes in adults. In children, PPV/SB is superior to PPV for anatomic and functional success at 1 year. In adults, the relief of traction by the GRT may reduce peripheral traction and obviate the need for an SB. However, in children, a supplemental SB can be beneficial as complete vitreous shaving and posterior hyaloid detachment, and postoperative positioning, are difficult in this group.


Subject(s)
Retinal Detachment , Retinal Perforations , Adult , Child , Humans , Infant , Retinal Detachment/diagnosis , Retinal Detachment/etiology , Retinal Detachment/surgery , Retinal Perforations/complications , Retinal Perforations/diagnosis , Retinal Perforations/surgery , Retrospective Studies , Scleral Buckling/adverse effects , Treatment Outcome , Visual Acuity , Vitrectomy/adverse effects
11.
Eur J Clin Invest ; 52(6): e13776, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35342931

ABSTRACT

BACKGROUND: SARS-CoV-2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two-step furin-mediated entry mechanism. Aprotinin is a broad-spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti-inflammatory properties for inhibiting the innate immunity contact system. METHODS: This was a multicentre, double-blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID-19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length of hospital stay and ICU admission. The secondary endpoints were each of the primary efficacy outcomes and a composite of oxygen therapy, analytical parameters and death. Safety outcomes included adverse reactions to treatment during a 30-day follow-up period. Treatment was given for 11 days or till discharge. RESULTS: With almost identical analytical profiles, significant differences were observed in treatment time, which was 2 days lower in the aprotinin group (p = .002), and length of hospital admission, which was 5 days shorter in the aprotinin group (p = .003). The incidence of discharge was 2.19 times higher (HR: 2.188 [1.182-4.047]) in the aprotinin group than in the placebo group (p = .013). In addition, the aprotinin-treated group required less oxygen therapy and had no adverse reactions or side effects. CONCLUSION: Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID-19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antiviral Agents/therapeutic use , Aprotinin/therapeutic use , Humans , Oxygen , Protease Inhibitors , Treatment Outcome
12.
Int Ophthalmol ; 42(3): 951-958, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34628544

ABSTRACT

PURPOSE: The purpose of this study was to report the 5-year outcomes of treatment-naive eyes with cystoid macular edema secondary to central retinal vein occlusion treated with intravitreal bevacizumab in routine clinical practice. METHODS: We conducted multicenter retrospective non-comparative case series of 102 eyes. The main outcome measured was the change in best-corrected visual acuity (BCVA) at 5 years. Secondary outcomes included the number of injections and the change in CMT at 5 years. RESULTS: At 5 years, the mean BCVA improved from 1.22 ± 0.58 (Snellen 20/428) at baseline to 1.00 ± 0.68 logMAR (Snellen 20/200; p < 0.0001). At 5 years, 48 (47%) eyes had a gain of ≥ 3 lines, 41 (40.2%) eyes remained within 3 lines and 13 (12.7%) eyes had a loss of ≥ 3 lines of BCVA. The CMT improved from 740 ± 243 to 322 ± 179 µm (p < 0.0001). At 5 years, 59 (57.8%) eyes had a completely dry SD-OCT. Patients received a total of 10.6 ± 6.1 (range 6-27) injections. Baseline BCVA (p < 0.0001) and the duration of symptoms prior to initial anti-VEGF injection (p = 0.0274) were the only predictive factors for BCVA at 5 years. CONCLUSIONS: After 5 years with an average of 10.6 injections, there was a mean gain of 0.22 logMAR. In addition, more eyes achieved a BCVA of ≥ 20/40, gained ≥ 3 lines and less patients had a BCVA ≤ 20/200. Eyes with a better baseline BCVA and a shorter duration of symptoms were more likely to achieve better BCVA at 5 years.


Subject(s)
Macular Edema , Retinal Vein Occlusion , Angiogenesis Inhibitors , Bevacizumab/therapeutic use , Humans , Intravitreal Injections , Macular Edema/diagnosis , Macular Edema/drug therapy , Macular Edema/etiology , Retina , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Vascular Endothelial Growth Factor A
13.
J Ophthalmol ; 2021: 5591865, 2021.
Article in English | MEDLINE | ID: mdl-34671489

ABSTRACT

PURPOSE: To assess the risk for capsular rupture during routine phacoemulsification in patients with a history of anti-VEGF injections and other possible risk modifiers such as treatment patterns, type of anti-VEGF agent, and experience of the surgeon, among others. METHODS: This study reviewed the medical records of 11,129 patients from 7 different hospitals in 5 countries. The study included 939 patients that underwent routine phacoemulsification and had a history of anti-VEGF therapy. We excluded patients with known risk factors for capsular rupture, as well as patients with a history of other retinal procedures. The study extracted data regarding general demographics, the number of previous injections, type of anti-VEGF agent, details of cataract surgery, and anti-VEGF treatment patterns. RESULTS: Overall prevalence of posterior capsular rupture: 7.45% (95% CI: 5.9-9.32%). The mean number of injections per patient was 3.37 ± 2.8. More than 50% of the patients received their last anti-VEGF injection within three months before cataract surgery. The complication rate during intravitreal injections was 1.07%. In the univariate analysis, the experience of the cataract surgeon (inexperience surgeons; OR: 2.93) and the history of prior anti-VEGF therapy (OR: 1.77) were significant risk indicators for PCR (p < 0.05). However, after controlling for age in the multivariate analysis, the trend did not reach a statistical significance. CONCLUSION: The risk for capsular rupture is higher in patients with a history of intravitreal anti-VEGF injections.

14.
Microorganisms ; 9(9)2021 Aug 26.
Article in English | MEDLINE | ID: mdl-34576707

ABSTRACT

Antimicrobial bacteria resistance is an important problem in children with recurrent urinary tract infections (rUTI), thus it is crucial to search for alternative therapies. Autologous bacterial lysates (ABL) may be a potential treatment for rUTI. Twenty-seven children with rUTI were evaluated for one year, urine and stool cultures were performed, 10 colonies of each culture were selected and those identified as Escherichia coli were characterized by serology. For patients who presented ≥105 UFC/mL, an ABL was manufactured and administered orally (1 mL/day) for a month. Twelve children were monitored for ≥1-year, 218 urine and 11 stool samples were analyzed. E. coli (80.5%) was the main bacteria isolated from urine and feces (72%). E. coli of classical urinary serotypes (UPEC), O25:H4, O75:HNM, and O9:HNM were identified in patients with persistent urinary infection (pUTI). In 54% of patients treated with ABL, the absence of bacteria was observed in urine samples after 3 months of treatment, 42% of these remained without UTI between 10-12 months. It was observed that the use of ABL controlled the infection for almost 1 year in more than 60% of the children. We consider it necessary to develop a polyvalent immunogen for the treatment and control of rUTI.

15.
Int J Mol Sci ; 22(11)2021 Jun 03.
Article in English | MEDLINE | ID: mdl-34205207

ABSTRACT

Since dysregulation of intracellular calcium (Ca2+) levels is a common occurrence in neurodegenerative diseases, including Alzheimer's disease (AD), the study of proteins that can correct neuronal Ca2+ dysregulation is of great interest. In previous work, we have shown that plasma membrane Ca2+-ATPase (PMCA), a high-affinity Ca2+ pump, is functionally impaired in AD and is inhibited by amyloid-ß peptide (Aß) and tau, two key components of pathological AD hallmarks. On the other hand, sorcin is a Ca2+-binding protein highly expressed in the brain, although its mechanism of action is far from being clear. Sorcin has been shown to interact with the intracellular sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), and other modulators of intracellular Ca2+ signaling, such as the ryanodine receptor or presenilin 2, which is closely associated with AD. The present work focuses on sorcin in search of new regulators of PMCA and antagonists of Aß and tau toxicity. Results show sorcin as an activator of PMCA, which also prevents the inhibitory effects of Aß and tau on the pump, and counteracts the neurotoxicity of Aß and tau by interacting with them.


Subject(s)
Alzheimer Disease/genetics , Calcium-Binding Proteins/genetics , Plasma Membrane Calcium-Transporting ATPases/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Alzheimer Disease/pathology , Amyloid beta-Peptides/genetics , Brain/metabolism , Brain/pathology , Calcium/metabolism , Calcium Signaling/genetics , Humans , Neurons/metabolism , Neurons/pathology , Plasma Membrane Calcium-Transporting ATPases/metabolism , Presenilin-2/genetics , Protein Binding/genetics , Protein Interaction Maps/genetics , tau Proteins/genetics
17.
Curr Opin Ophthalmol ; 32(3): 203-208, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33770016

ABSTRACT

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the leading causes of preventable vision loss in the world and its prevalence continues to increase worldwide. One of the ultimate and visually impairing complications of DR is proliferative diabetic retinopathy (PDR) and subsequent tractional retinal detachment. Treatment modalities, surgical techniques, and a better understanding of the pathophysiology of DR and PDR continue to change the way we approach the disease. The goal of this review is to provide an update on recent treatment modalities and outcomes of proliferative diabetic retinopathy and its complications including tractional retinal detachment. RECENT FINDINGS: Panretinal photocoagulation (PRP), anti-vascular endothelial growth factor (anti-VEGF), and pars plana vitrectomy are the mainstay of PDR treatment. However, PRP and anti-VEGF are associated with significant treatment burden and multiple subsequent treatments. Early vitrectomy is associated with vision preservation, less treatment burden, and less subsequent treatments than therapy with PRP and anti-VEGF. SUMMARY: Concerning costs, high rates of noncompliance in the diabetic population and significant rates of subsequent treatments with initial PRP and anti-VEGF, early vitrectomy for diabetic retinopathy in patients at risk of PDR is a cost-effective long-term stabilizing treatment for diabetics with advanced disease.


Subject(s)
Diabetic Retinopathy/surgery , Retinal Detachment/surgery , Retinal Neovascularization/surgery , Vitrectomy/methods , Angiogenesis Inhibitors/therapeutic use , Diabetic Retinopathy/complications , Diabetic Retinopathy/drug therapy , Humans , Laser Coagulation/methods , Retinal Detachment/drug therapy , Retinal Detachment/etiology , Retinal Neovascularization/complications , Retinal Neovascularization/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors
18.
J Pers Med ; 10(4)2020 Dec 18.
Article in English | MEDLINE | ID: mdl-33352925

ABSTRACT

Antipsychotics are the keystone of the treatment of severe and prolonged mental disorders. However, there are many risks associated with these drugs and not all patients undergo full therapeutic profit from them. The application of the 5 Step Precision Medicine model(5SPM), based on the analysis of the pharmacogenetic profile of each patient, could be a helpful tool to solve many of the problematics traditionally associated with the neuroleptic treatment. In order to solve this question, a cohort of psychotic patients that showed poor clinical evolution was analyzed. After evaluating the relationship between the prescribed treatment and pharmacogenetic profile of each patient, a great number of pharmacological interactions and pharmacogenetical conflicts were found. After reconsidering the treatment of the conflictive cases, patients showed a substantial reduction on mean daily doses and polytherapy cases, which may cause less risk of adverse effects, greater adherence, and a reduction on economic costs.

19.
Graefes Arch Clin Exp Ophthalmol ; 258(9): 1857-1861, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32409979

ABSTRACT

PURPOSE: To report our experience in non-contact wide-angled visualization with chandelier-assisted scleral buckling (SB) in uncomplicated primary rhegmatogenous retinal detachments (RRD). METHODS: Retrospective case series of 282 eyes that underwent non-contact wide-angled visualization with chandelier-assisted SB and were followed for a mean of 13.5 months. RESULTS: There were 160 male patients. The average age was 42.6 years old. There were 262 eyes that were phakic, 18 pseudophakic, and 2 aphakic. Two-thirds of eyes presented with the macula detached. Eyes had an average of 1.6 breaks. The single operation anatomic success rate was 85.1% (240/282). The pre-op visual acuity improved from 1.21 to 0.76 logMAR at 6 months (p < 0.0001). Complications included a case of scleral laceration, choroidal hemorrhage, 3 epiretinal membranes, 1 macular fold, and 4 eyes with buckle exposure. CONCLUSION: Non-contact wide-angled visualization with chandelier-assisted SB compares favorably with conventional SB for primary uncomplicated primary RRD.


Subject(s)
Gonioscopy/methods , Retinal Detachment/surgery , Scleral Buckling/methods , Surgery, Computer-Assisted/methods , Visual Acuity , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Retinal Detachment/diagnosis , Retrospective Studies , Treatment Outcome , Young Adult
20.
Curr Opin Ophthalmol ; 31(3): 185-191, 2020 May.
Article in English | MEDLINE | ID: mdl-32235251

ABSTRACT

PURPOSE OF REVIEW: To compare outcomes of 27-gauge and 23-gauge pars plana vitrectomy (PPV) for treatment of vitreoretinal diseases. RECENT FINDINGS: Sixty-eight patients undergoing microincisional PPV for treatment of vitreoretinal diseases were randomized 1 : 1 to 27-gauge or 23-gauge surgery with a 7500 cuts-per-minute vitrectomy probe. The most common reasons for vitrectomy were epiretinal membrane (49%) and vitreous hemorrhage (24%). Mean ±â€Šstandard deviation (SD) changes from immediate preoperative to immediate postoperative intraocular pressure were -0.40 ±â€Š6.60 mmHg in the 27-gauge and -3.05 ±â€Š7.64 mmHg in the 23-gauge group (adjusted mean difference 2.42 mmHg, 95% lower confidence limit 0.64, P = 0.013), but these changes were not associated with primary reason for vitrectomy (P = 0.065). Mean ±â€ŠSD conjunctival edema grades in the 27-gauge and 23-gauge groups 1 week after surgery were 0.02 ±â€Š0.124 and 0.10 ±â€Š0.246, respectively (least squares mean difference -0.09, 95% upper confidence limit -0.03, P = 0.004), and were 0.01 ±â€Š0.122 and 0.12 ±â€Š0.338, respectively, at the probe incision site. Conjunctival edema grades were similar in both groups at 1 and 3 months. Mean ±â€ŠSD pain ratings on postoperative day 1 - an indicator of patient comfort - were similar in the two groups. SUMMARY: Smaller diameter vitrectomy instruments are associated with smaller reductions in immediate postoperative intraocular pressure.


Subject(s)
Epiretinal Membrane/surgery , Vitrectomy/instrumentation , Vitreous Hemorrhage/surgery , Epiretinal Membrane/physiopathology , Humans , Intraocular Pressure/physiology , Treatment Outcome , Visual Acuity/physiology , Vitreoretinal Surgery , Vitreous Hemorrhage/physiopathology
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