Harnessing diversity to study Alzheimer's disease: A new iPSC resource from the NIH CARD and ADNI.

The iDA Project (iPSCs to Study Diversity in Alzheimer's and Alzheimer's Disease-related Dementias) is generating 200 induced pluripotent stem cell lines from Alzheimer's Disease Neuroimaging Initiative participants. These lines are sex balanced, include common APOE genotypes, span disease stages, and are ancestrally diverse. Cell lines and characterization data will be shared openly.

A fully automated FAIMS-DIA mass spectrometry-based proteomic pipeline.

Here, we present a standardized, "off-the-shelf" proteomics pipeline working in a single 96-well plate to achieve deep coverage of cellular proteomes with high throughput and scalability. This integrated pipeline streamlines a fully automated sample preparation platform, a data-independent acquisition (DIA) coupled with high-field asymmetric waveform ion mobility spectrometer (FAIMS) interface, and an optimized library-free DIA database search strategy. Our systematic evaluation of FAIMS-DIA showing single compensation voltage (CV) at -35 V not only yields the deepest proteome coverage but also best correlates with DIA without FAIMS. Our in-depth comparison of direct-DIA database search engines shows that Spectronaut outperforms others, providing the highest quantifiable proteins. Next, we apply three common DIA strategies in characterizing human induced pluripotent stem cell (iPSC)-derived neurons and show single-shot mass spectrometry (MS) using single-CV (-35 V)-FAIMS-DIA results in >9,000 quantifiable proteins with <10% missing values, as well as superior reproducibility and accuracy compared with other existing DIA methods.

iPSC motor neurons, but not other derived cell types, capture gene expression changes in postmortem sporadic ALS motor neurons.

Motor neuron degeneration, the defining feature of amyotrophic lateral sclerosis (ALS), is a primary example of cell-type specificity in neurodegenerative diseases. Using isogenic pairs of induced pluripotent stem cells (iPSCs) harboring different familial ALS mutations, we assess the capacity of iPSC-derived lower motor neurons, sensory neurons, astrocytes, and superficial cortical neurons to capture disease features including transcriptional and splicing dysregulation observed in human postmortem neurons. At early time points, differentially regulated genes in iPSC-derived lower motor neurons, but not other cell types, overlap with one-third of the differentially regulated genes in laser-dissected motor neurons from ALS compared with control postmortem spinal cords. For genes altered in both the iPSC model and bona fide human lower motor neurons, expression changes correlate between the two populations. In iPSC-derived lower motor neurons, but not other derived cell types, we detect the downregulation of genes affected by TDP-43-dependent splicing. This reduction takes place exclusively within genotypes known to involve TDP-43 pathology.

Amino acid homeostasis is a target of metformin therapy.

OBJECTIVE: Unexplained changes in regulation of branched chain amino acids (BCAA) during diabetes therapy with metformin have been known for years. Here we have investigated mechanisms underlying this effect. METHODS: We used cellular approaches, including single gene/protein measurements, as well as systems-level proteomics. Findings were then cross-validated with electronic health records and other data from human material. RESULTS: In cell studies, we observed diminished uptake/incorporation of amino acids following metformin treatment of liver cells and cardiac myocytes. Supplementation of media with amino acids attenuated known effects of the drug, including on glucose production, providing a possible explanation for discrepancies between effective doses in vivo and in vitro observed in most studies. Data-Independent Acquisition proteomics identified that SNAT2, which mediates tertiary control of BCAA uptake, was the most strongly suppressed amino acid transporter in liver cells following metformin treatment. Other transporters were affected to a lesser extent. In humans, metformin attenuated increased risk of left ventricular hypertrophy due to the AA allele of KLF15, which is an inducer of BCAA catabolism. In plasma from a double-blind placebo-controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin caused selective accumulation of plasma BCAA and glutamine, consistent with the effects in cells. CONCLUSIONS: Metformin restricts tertiary control of BCAA cellular uptake. We conclude that modulation of amino acid homeostasis contributes to therapeutic actions of the drug.

Mpox Vaccine Interest Survey Prioritization and Data Flow: Maricopa County, Arizona, July-August 2022.

With increasing mpox cases in Maricopa County, Arizona, the county's health department launched a survey on July 11, 2022, to gather eligibility and contact data and provide clinic information to those interested in JYNNEOS as postexposure prophylaxis (PEP) or expanded postexposure prophylaxis(PEP++). Survey data were matched to case and vaccination data. Overall, 343 of the 513 respondents (66.9%) who reported close contact with an mpox case patient received PEP and 1712 of the 3379 respondents (50.7%) who were unsure of their contact status received PEP++. This outreach intervention connected potential close contacts unknown to MCDPH with PEP or PEP++. (Am J Public Health. 2023;113(5):504-508. https://doi.org/10.2105/AJPH.2023.307224).

A reference human induced pluripotent stem cell line for large-scale collaborative studies.

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.

Effect of chronic administration of 17ß-estradiol on the vasopressor responses induced by the sympathetic nervous system in insulin resistance rats.

Several studies have demonstrated that the underlying mechanism of insulin resistance (IR) is linked with developing diseases like diabetes mellitus, hypertension, metabolic syndrome, and polycystic ovary syndrome. In turn, the dysfunction of female gonadal hormones (especially 17ß-estradiol) may be related to the development of IR complications since different studies have shown that 17ß-estradiol has a cardioprotector and vasorelaxant effect. This study aimed was to determine the effect of the 17ß-estradiol administration in insulin-resistant rats and its effects on cardiovascular responses in pithed rats. Thus, the vasopressor responses are induced by sympathetic stimulation or i.v. bolus injections of noradrenaline (α1/2), methoxamine (α1), and UK 14,304 (α2) adrenergic agonist were determined in female pithed rats with fructose-induced insulin resistance or control rats treated with: 1) 17ß-estradiol or 2) its vehicle (oil) for 5 weeks. Thus, 17ß-estradiol decreased heart rate, prevented the increase of blood pressure induced by ovariectomy, but with the opposite effect on sham-operated rats; and decreased vasopressor responses induced by i.v. bolus injections of noradrenaline on sham-operated (control and fructose group) and ovariectomized (control) rats, and those induced by i.v. bolus injections of methoxamine (α1 adrenergic agonist). Overall, these results suggest 17ß-estradiol has a cardioprotective effect, and its effect on vasopressor responses could be mediated mainly by the α1 adrenergic receptor. In contrast, IR with ovariectomy 17ß-estradiol decreases or loses its cardioprotector effect, this could suggest a possible link between the adrenergic receptors and the insulin pathway.

Prevalencia de afecciones musculoesqueléticas y factores asociados en adultos mayores en una Fundación de Duran / Prevalence of musculoskeletal conditions and associated factors in older adults in a Duran Foundation / Prevalência de condições musculoesqueléticas e fatores associados em idosos de uma Fundação Duran

Las afecciones musculoesqueléticas comprenden trastornos degenerativos que aparecen principalmente en personas de edad avanzada, deteriorando significativamente la salud, debido a que están relacionadas con dolor muscular u óseo, alteraciones del movimiento, mayor riesgo de caídas, fracturas y capacidad alterada para realizar las actividades del diario vivir. Objetivo. Determinar la prevalencia de afecciones musculo esqueléticas y factores asociados en el adulto mayor que asistieron a la Fundación. Metodología. Con enfoque cuantitativo, descriptivo, transversal, no experimental y retrospectivo. Los instrumentos a utilizar incluyeron el dinamómetro, índice de masa corporal y la antropometría. Resultados. se determinó que la prevalencia de las alteraciones musculoesqueléticas fue del 59%, de los cuales, la artrosis de rodilla fue la más común con una prevalencia del 90%, asociados con un índice de masa corporal elevado con un valor mayor a 25 kg/m2 y una fuerza muscular disminuida con un valor menor a 28.2 kg para los hombres y menor a 15.4 kg para las mujeres. En contraste, las medidas antropométricas fueron normales, con valores mayor o igual a 31 cm para la circunferencia de la pantorrilla y mayor o igual a 22 cm para la circunferencia del brazo. Conclusión. Existe una alta prevalencia de alteraciones musculoesqueléticas, El sobrepeso y la debilidad muscular fueron los únicos factores asociados.

Musculoskeletal disorders include degenerative disorders that appear mainly in elderly people, significantly deteriorating their health, because they are related to muscle or bone pain, movement disorders, increased risk of falls, fractures and impaired ability to perform daily activities. Objective. To determine the prevalence of musculoskeletal disorders and associated factors in older adults attending the Fundación. Methodology. With a quantitative, descriptive, cross-sectional, non-experimental and retrospective approach. The instruments to be used included the dynamometer, body mass index and anthropometry. Results. It was determined that the prevalence of musculoskeletal alterations was 59%, of which knee osteoarthritis was the most common with a prevalence of 90%, associated with an elevated body mass index with a value greater than 25 kg/m2 and decreased muscle strength with a value of less than 28.2 kg for men and less than 15.4 kg for women. In contrast, anthropometric measurements were normal, with values greater than or equal to 31 cm for calf circumference and greater than or equal to 22 cm for arm circumference. Conclusion. There is a high prevalence of musculoskeletal alterations. Overweight and muscle weakness were the only associated factors

As condições musculoesqueléticas compreendem desordens degenerativas que ocorrem principalmente em pessoas idosas, prejudicando significativamente a saúde, pois estão associadas a dores musculares ou nos ossos, comprometimento dos movimentos, aumento do risco de quedas, fraturas e incapacidade de realizar atividades da vida diária. Objetivo. Para determinar a prevalência de distúrbios musculoesqueléticos e fatores associados em adultos idosos que frequentam a Fundação. Metodologia. Com uma abordagem quantitativa, descritiva, transversal, não-experimental e retrospectiva. Os instrumentos utilizados incluíam o dinamômetro, o índice de massa corporal e a antropometria. Resultados. Foi determinado que a prevalência de distúrbios musculoesqueléticos foi de 59%, dos quais a osteoartrose do joelho foi a mais comum com uma prevalência de 90%, associada a um alto índice de massa corporal com um valor superior a 25 kg/m2 e uma diminuição da força muscular com um valor inferior a 28,2 kg para homens e inferior a 15,4 kg para mulheres. Em contraste, as medidas antropométricas foram normais, com valores maiores ou iguais a 31 cm para a circunferência da barriga da perna e maiores ou iguais a 22 cm para a circunferência do braço. Conclusão. Há uma alta prevalência de distúrbios musculoesqueléticos. O excesso de peso e a fraqueza muscular foram os únicos fatores associados.

Prosthetic Valve Endocarditis From Trichosporon asahii in an Immunocompetent Patient.

Fungal endocarditis is a rare clinical entity. This report describes an unusual case of fungal endocarditis caused by infection with Trichosporon asahii in a 20-year-old immunocompetent man who received the diagnosis 1 year following biological aortic valve replacement. (Level of Difficulty: Beginner.).

Spinal TASK-1 and TASK-3 modulate inflammatory and neuropathic pain.

This study assessed the participation of spinal TWIK-related acid-sensitive K+ channels 1 and 3 (TASK-1 and TASK-3) in inflammatory (formalin test) and neuropathic (spinal nerve ligation, SNL) pain in rats. Intrathecal pre-treatment (-10 min) with the TASK-1 blocker ML365 or TASK-3 blocker PK-THPP, but not vehicle, enhanced in a dose-dependent manner 1% formalin-induced acute and long-lasting secondary mechanical allodynia and mechanical hyperalgesia in rats. In contrast, intrathecal pre-treatment with terbinafine, an activator of TASK-3, reduced formalin-induced flinching and allodynia/hyperalgesia. Both blockers and terbinafine had similar effects on female and male rats. In addition, intrathecal injection of ML365 or PK-THPP blocked the terbinafine-induced antiallodynic effect in neuropathic rats, but they did not modify baseline withdrawal threshold in naïve or sham-operated rats. TASK-1 and TASK-3 mRNA and protein were expressed in L4 and L5 dorsal root ganglia (DRG) and dorsal and ventral spinal cord of naïve animals. Interestingly, formalin injection increased TASK-1 expression in ipsilateral L5 DRG, but not in the spinal cord. Moreover, formalin injection transiently enhanced TASK-3 expression in ipsilateral L5 DRG and dorsal spinal cord. In contrast, SNL down-regulated TASK-3 expression in the ipsilateral L4 and L5 DRG but not in dorsal or ventral spinal cord, while SNL did not modify TASK-1 expression at any tissue. The pharmacological and molecular results suggest that TASK-1 and TASK-3 have a relevant antinociceptive role in inflammatory and neuropathic pain.

Fructose-Induced Insulin Resistance as a Model of Neuropathic Pain in Rats.

Peripheral neuropathy is one of the main complications of diabetes. The pathogenesis of this affectation is not completely understood. Several studies refer to hyperglycemia as the principal cause of diabetic neuropathy. Nonetheless, there are changes in the expression of insulin receptor during the progress of diabetic neuropathy, suggesting that this disorder begins before high glucose blood levels are established. In this study, we investigated fructose-induced insulin resistance as a model of neuropathic pain. Insulin resistance was induced by 15% fructose in drinking water for 16 weeks. Fructose slightly enhanced blood glucose levels. In contrast, chronic fructose increased insulin plasma levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index. Moreover, fructose induced hyperalgesia (to 0.5% formalin) and tactile allodynia. Interestingly, gabapentin and metformin, but not diclofenac, reversed in a dose-dependent manner fructose-induced tactile allodynia. Fructose enhanced activating factor transcription 3 (ATF3), but not caspase-3 and α2δ-1 subunit, in individual L4 and L5 dorsal root ganglia (DRG) and sciatic nerve. Chronic fructose also increased anoctamin-1 and ASIC3 whereas it reduced insulin receptor-ß, α5GABAA receptors and TASK-3 channels protein expression in DRG and sciatic nerve. In contrast, fructose did not change TRPV1 channel protein expression. Treatment with metformin for 4 weeks reversed some of the fructose-induced changes in protein expression. Taken together, these data suggest that insulin resistance induced by fructose reproduces several aspects of neuropathic-like pain. Our data also suggest that nociceptive hypersensitivity in this model is due to the modulation of several ionic channels at the primary afferent neurons.

Conocimientos, actitudes y prácticas frente al control del vector Aedes aegypti, Villanueva-Casanare, Colombia, 2016 / Knowledges, attitudes and practices in front the control of the vector Aedes aegypti, Villanueva-Casanare, Colombia, 2016

Objetivo. Identificar, para Villanueva, los conocimientos, actitudes y prácticas (CAP) de la comunidad frente a enfermedades transmitidas por Aedes aegypti sus factores de riesgo, signos, síntomas asociados con las enfermedades y, medidas de prevención. Métodos. Estudio transversal. Muestreo aleatorio por conglomerados. Análisis realizado mediante estadística descriptiva con Epi-Info 7.2.0. Resultados. 211 encuestas diligenciadas; mujeres 155(73,5%). Edad promedio 34,2±17,2(rango 10-85) años, tiempo medio de permanencia en el municipio 19,2±16,8(rango 1-78) años. Conocimiento sobre rol transmisor del mosquito osciló entre 76,8%-90,5%; desconocimiento sobre signos y síntomas causados por estas enfermedades osciló entre 90%-100. Se encontró bajo conocimiento (8,5%-28,0%) y bajo uso (4,7%-27,0%) de medidas de control basadas en acciones individuales/colectivas. La medida estatal/gubernamental de control más recordada fue fumigación (42,2%). Conclusiones. Existe un conocimiento somero sobre el vector y las enfermedades. Se precisan acciones decididas a través de la movilización social, un acompañamiento intensivo de las comunidades.

Objective. To dentify in Villanueva’s people their knowledges, attitudes and practices (KAP) about diseases transmitted by Aedes aegypti - Dengue, Chikungunya and Zika viruses, their risk factors, disease-associated signs and symptoms, and individual or collective measures against them. Methods. Cross-sectional. Analysis performed using descriptive statistics with Epi-Info 7.2.0. Results. 211 forms completed; women 155(73.5%), mean age 34,2±17,2 years (range 10-85). Mean residence time in the municipality 19.2±16.8 years (range 1-78). Knowledge about the transmission role of the mosquito oscillates between 76.8%-90.5%; ignorance about their signs and symptoms goes between 90%-100%. We found low knowledge (8.5%-28.0%) and low use (4.7%-27.0%) of prevention/control measures based upon individual or collective actions; 57.8% were not visited by a health worker in the last six months. Most remembered Public Health control measure by respondents was fumigation (42.2%). Conclusions. There is lack of knowledge about both vector and its related diseases. Strong, focused actions by health authority are needed through social mobilization, intensive communities’ support and empowerment.

Pharmacological evaluation of metformin and N-benzylbiguanide, a novel analogue of metformin, on the vasopressor responses to adrenergic system stimulation in pithed rats with fructose-induced insulin resistance.

Metformin has been associated with cardioprotection, vasorelaxation and normalization of endothelial function during type 2 Diabetes Mellitus. However, few studies have analysed its effects on vascular adrenergic system. Our study has evaluated the vasopressor responses induced by sympathetic stimulation or by i.v. bolus injections of the agonists noradrenaline (α1/2), methoxamine (α1) and UK 14,304 (α2) in rats with fructose-induced insulin resistance chronically pretreated with either metformin or EGL-6M (N-benzylbiguanide), a novel analogue of metformin. Rats were treated with fructose (15%) or tap water (control) during 16 weeks. Next, both groups were treated daily during 4 weeks with: (1) vehicle; (2) metformin (50mg/kg); or (3) EGL-6M (50mg/kg). Blood glucose and plasma insulin were determined before and after administration of glucose during oral glucose tolerance test. Animals treated with fructose showed hyperinsulinemia and insulin resistance, which were decreased by metformin and EGL-6M. In animals treated with fructose, the vasopressor responses induced by: (1) sympathetic stimulation were decreased; (2) noradrenaline were increased; and (3) methoxamine and UK 14,304 remained unaffected compared with control group. In control animals, metformin failed to modify the vasopressor responses analysed, while EGL-6M increased the vasopressor responses to sympathetic stimulation. In rats treated with fructose, metformin decreased vasopressor response to noradrenaline but did not modify the sympathetic stimulation responses. EGL-6M increased the vasopressor responses to sympathetic stimulation without modifying those to noradrenaline, methoxamine or UK 14,304. Collectively, these data suggest that EGL-6M is capable to increase insulin sensitivity and the vasopressor sympathetic outflow in rats.

Pharmacological evidence that NaHS inhibits the vasopressor responses induced by stimulation of the preganglionic sympathetic outflow in pithed rats.

It has been reported that i.v. administration of NaHS, a donor of H2S, elicited dose-dependent hypotension although the mechanisms are not completely understood. In this regard, several mechanisms could be involved including the inhibition of the vasopressor sympathetic outflow. Thus, this study was designed to determine the potential capability of NaHS to mediate inhibition of the vasopressor responses induced by preganglionic sympathetic stimulation. For this purpose, Wistar rats were anaesthetised, pithed and cannulated for drug administration. In animals pre-treated with gallamine, the effect of i.v. infusion of NaHS (310 and 560µg/kgmin) or its vehicle (phosphate buffer) was determined on the vasopressor responses induced by: (1) sympathetic stimulation (0.03-10Hz); (2) i.v. bolus injections of exogenous noradrenaline (0.03-3µg/kg); or (3) methoxamine (1-100µg/kg). The vasopressor responses induced by preganglionic sympathetic stimulation were dose-dependently inhibited by i.v. infusion of NaHS (310 and 560µg/kgmin), but not by vehicle, particularly at high frequencies. In marked contrast, the vasopressor responses to exogenous noradrenaline or methoxamine were not inhibited by the above doses of NaHS or its vehicle. The above results, taken together, demonstrate that NaHS inhibited the vasopressor responses induced by preganglionic sympathetic outflow by a prejunctional mechanism. This is the first evidence demonstrating this effect by NaHS that may contribute, at least in part, to the hypotension induced by NaHS.

Pharmacological characterization of the mechanisms involved in the vasorelaxation induced by progesterone and 17ß-estradiol on isolated canine basilar and internal carotid arteries.

Progesterone and 17ß-estradiol induce vasorelaxation through non-genomic mechanisms in several isolated blood vessels; however, no study has systematically evaluated the mechanisms involved in the relaxation induced by 17ß-estradiol and progesterone in the canine basilar and internal carotid arteries that play a key role in cerebral circulation. Thus, relaxant effects of progesterone and 17ß-estradiol on KCl- and/or PGF2α-pre-contracted arterial rings were investigated in absence or presence of several antagonists/inhibitors/blockers; the effect on the contractile responses to CaCl2 was also determined. In both arteries progesterone (5.6-180 µM) and 17ß-estradiol (1.8-180 µM): (1) produced concentration-dependent relaxations of KCl- or PGF2α-pre-contracted arterial rings; (2) the relaxations were unaffected by actinomycin D (10 µM), cycloheximide (10 µM), SQ 22,536 (100 µM) or ODQ (30 µM), potassium channel blockers and ICI 182,780 (only for 17ß-estradiol). In the basilar artery the vasorelaxation induced by 17ß-estradiol was slightly blocked by tetraethylammonium (10mM) and glibenclamide (KATP; 10 µM). In both arteries, progesterone (10-100 µM), 17ß-estradiol (3.1-31 µM) and nifedipine (0.01-1 µM) produced a concentration-dependent blockade of the contraction to CaCl2 (10 µM-10mM). These results suggest that progesterone and 17ß-estradiol produced relaxation in the basilar and internal carotid arteries by blockade of L-type voltage dependent Ca(2+) channel but not by genomic mechanisms or production of cAMP/cGMP. Potassium channels did not play a role in the relaxation to progesterone in both arteries or in the effect of 17ß-estradiol in the internal carotid artery; meanwhile KATP channels play a minor role on the effect of 17ß-estradiol in the basilar artery.

Pharmacological evidence that 5-HT1A/1B/1D, α2-adrenoceptors and D2-like receptors mediate ergotamine-induced inhibition of the vasopressor sympathetic outflow in pithed rats.

The sympathetic nervous system that innervates the peripheral circulation is regulated by several mechanisms/receptors. It has been reported that prejunctional 5-HT1A, 5-HT1B, 5-HT1D, D2-like receptors and α2-adrenoceptors mediate the inhibition of the vasopressor sympathetic outflow in pithed rats. In addition, ergotamine, an antimigraine drug, displays affinity at the above receptors and may explain some of its adverse/therapeutic effects. Thus, the aims of this study were to investigate in pithed rats: (i) whether ergotamine produces inhibition of the vasopressor sympathetic outflow; and (ii) the major receptors involved in this effect. For this purpose, male Wistar pithed rats were pre-treated with gallamine (25 mg/kg; i.v.) and desipramine (50 µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T9; 0.03-3 Hz) or to receive i.v. bolus of exogenous noradrenaline (0.03-3 µg/kg). I.v. continuous infusions of ergotamine (1 and 1.8 µg/kgmin) dose-dependently inhibited the vasopressor responses to sympathetic stimulation but not those to exogenous noradrenaline. The sympatho-inhibition elicited by 1.8 µg/kg min ergotamine was (i) unaffected by saline (1 ml/kg); (ii) partially antagonised by WAY 100635 (5-HT1A; 30 µg/kg) and rauwolscine (α2-adrenoceptor; 300 µg/kg), and (iii) dose-dependently blocked by GR 127935 (5-HT1B/1D; 100 and 300 µg/kg) or raclopride (D2-like; 300 and 1000 µg/kg), The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. The above results suggest that ergotamine induces inhibition of the vasopressor sympathetic outflow by activation of prejunctional 5-HT1A, 5-HT1B/1D, α2-adrenoceptors and D2-like receptors in pithed rats.

Granule cells born in the adult rat hippocampus can regulate the expression of GABAergic markers.

The granule cells (GCs) of the dentate gyrus transiently express markers of the GABAergic phenotype early during development. However, GCs are generated throughout life, posing the question of whether the newborn neurons in the adult rodent recapitulate the development of the neurotransmitter phenotype of GCs generated during embryonic and early postnatal development. In this work we asked whether newborn GCs transiently express a GABAergic phenotype during their development in the adult rat. Using retroviral infection, we labeled dividing cells in the dorsal hippocampus with GFP, identified them as granule cells, and determined their expression of GABAergic markers at different developmental stages. We found that GFP-positive cells express Prox-1 and calbindin, identifying them as GCs. GABA or GAD(67) was expressed in 13% of GFP-positive cells at 7 dpi, in 16% at 10 dpi and in 20% at 15 dpi. At 30 dpi, however, no GFP-positive cell somata containing GABAergic markers were detected, but their mossy fiber boutons did contain GAD(67). Interestingly, developing GCs detected with doublecortin and PSA-NCAM in non-injected adult rats, did not express GABAergic markers, suggesting that retroviral injection/infection stimulates their transient expression. However, in non-injected rats, a number of mossy fiber boutons of newborn granule cells detected with PSA-NCAM did express GAD(67). Our findings reveal that developing GCs born in the adult are able to transiently up-regulate the expression of GABAergic markers to be detected in their soma in response to insults, while they constitutively express GAD(67) in their mossy fibers.

Factores de riesgo en el paciente con candidemia / Risk factors in the candidemia patient

Antecedentes: en la actualidad al hongo del género Candida se le considera un germen patógeno común y destructor. Objetivo: estudiar las características epidemiológicas y factores de riesgo de la candidemia en un hospital de enseñanza con 152 camas. Material y métodos: se realizó un estudio de casos y controles, mediante la revisión de los expedientes de los pacientes que desarrollaron cuadro clínico de sepsis y a quienes se hizo aislamiento de Candida en un hemocultivo en el periodo de 1990 a 1997. Se obtuvieron los aspectos demográficos y se estudiaron los factores de riesgo, comparándolos con los de un grupo control de dos por caso. Resultados: los 31 casos detectados correspondieron a una incidencia de 0.39/1,000 egresos; dos terceras partes aparecieron a partir de 1995. El 78.5 por ciento de los pacientes se encontraban en la unidad de terapia intensiva (UTI) al momento del cuadro de candidemia y otro porcentaje similar tenía más de 15 días de estancia. Destacaron otros factores predisponentes, como el uso de vancomicina e imipenem, procedimientos médico-quirúrgicos del tubo digestivo y el uso de catéteres y sondas. Conclusiones: la incidencia de candidemia resultó igual a la reportada para pequeños hospitales de enseñanza, como el nuestro, y la mayor parte de los casos ocurrieron en los últimos años. A pesar de que los factores predisponentes son conocidos, consideramos que deben implantarse medidas estrictas de aislamiento, como una vigilancia estrecha del enfermo que se encuentre en la UTI por largos periodos, un control adecuado del uso de antibióticos y la realización de estudios prospectivos para detectar de manera oportuna los casos y administrar un tratamiento temprano.