Fibroblast growth factor 2 (FGF2) is present in human spermatozoa and is related with sperm motility. The use of recombinant FGF2 to improve motile sperm recovery.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate several functions of somatic cells. In a previous work, we reported FGFR expression in human spermatozoa and their involvement in motility. This study aimed to evaluate the presence and localization of fibroblast growth factor 2 (FGF2) in human spermatozoa, to determine the relationship of FGF2 levels with conventional semen parameters and to assess the effect of recombinant FGF2 (rFGF2) on sperm recovery in a selection procedure. Western immunoblotting analysis using an antibody against FGF2 revealed an 18-kDa band in sperm protein extracts. The protein was immunolocalized in the sperm flagellum and acrosomal region, as well as in all germ cells. Sperm FGF2 levels, assessed by flow cytometry, showed a positive (p < 0.05) correlation with sperm concentration, motility, total sperm number and total motile cells per ejaculate. Moreover, samples with abnormal motility depicted diminished (p < 0.01) FGF2 levels compared to those with normal motility. Spermatozoa exposed to rFGF2 bound the protein, exhibited higher (p < 0.05) total and motile sperm recoveries, and increased (p < 0.01) kinematic parameters after the swim-up. Findings herein presented lead to consider sperm FGF2 level as a potential marker of sperm quality, and rFGF2 as a supplement for improving sperm recovery in selection techniques.

Successful Implementation of Clinical Information Technology: Seven Key Lessons from CPOE.

OBJECTIVES: To identify and describe the most critical strategic and operational contributors to the successful implementation of clinical information technologies, as deployed within a moderate sized system of U.S. community hospitals. BACKGROUND AND SETTING: CHRISTUS Health is a multi-state system comprised of more than 350 services and 60 hospitals with over 9 000 physicians. The Santa Rosa region of CHRISTUS Health, located in greater San Antonio, Texas is comprised of three adult community hospital facilities and one Children's hospital each with bed capacities of 142-180. Computerized Patient Order Entry (CPOE) was first implemented in 2012 within a complex market environment. The Santa Rosa region has 2 417 credentialed physicians and 263 mid-level allied health professionals. METHODS: This report focuses on the seven most valuable strategies deployed by the Health Informatics team in a large four hospital CHRISTUS region to achieve strong CPOE adoption and critical success lessons learned. The findings are placed within the context of the literature describing best practices in health information technology implementation. RESULTS: While the elements described involved discrete de novo process generation to support implementation and operations, collectively they represent the creation of a new customer-centric service culture in our Health Informatics team, which has served as a foundation for ensuring strong clinical information technology adoption beyond CPOE. CONCLUSION: The seven success factors described are not limited in their value to and impact on CPOE adoption, but generalize to - and can advance success in - varied other clinical information technology implementations across diverse hospitals. A number of these factors are supported by reports in the literature of other institutions' successful implementations of CPOE and other clinical information technologies, and while not prescriptive to other settings, may be adapted to yield value elsewhere.

p76(MDM2) inhibits the ability of p90(MDM2) to destabilize p53.

The mdm2 oncogene encodes p90(MDM2), which binds to and inactivates the p53 tumor suppressor protein. p90(MDM2) inhibits p53 by blocking the transcriptional activation domain of p53 as well as by stimulating its degradation. Recently, we showed that another product of the wild-type mdm2 gene, p76(MDM2), lacks the first 49 amino acids of p90(MDM2) and cannot bind p53. Here, we report that, like p90(MDM2), p76(MDM2) is expressed in both the nuclear and cytoplasmic compartments. Overexpression of p76(MDM2) antagonizes the ability of p90(MDM2) to stimulate the degradation of p53 and leads to an increase in the levels and activity of p53. Seven murine tissues express an alternatively spliced mdm2 mRNA that can encode p76(MDM2) but not p90(MDM2), as well as the normally spliced mdm2 mRNA that encodes both MDM2 proteins. All seven tissues express both MDM2 proteins. p90(MDM2) is much more abundant than p76(MDM2) in the testis, brain, heart, and kidney. However, in those tissues known to undergo p53-mediated apoptosis in response to gamma-irradiation, the thymus, spleen, and intestine, the levels of the MDM2 proteins are roughly equivalent. Our results indicate that the ratio of the two MDM2 proteins may regulate the response of tissues to DNA damage.

The E7 oncoprotein of human papillomavirus type 16 stabilizes p53 through a mechanism independent of p19(ARF).

High-risk human papillomaviruses are causally associated with cervical cancer. Two viral oncogenes, E6 and E7, are expressed in most cervical cancers, and these genes cause cancer when expressed in experimental animals. The E6 protein targets the p53 tumor suppressor for degradation, while the E7 protein inactivates the retinoblastoma susceptibility protein (pRb), in part by stimulating its degradation. In contrast, expression of E7 in the absence of E6 leads to stabilization of p53. Here we show that E7 stabilizes p53 in mouse embryo fibroblasts lacking p19(ARF). The stable p53 is active as a transcriptional activator, as evidenced by the increased expression of the p53-responsive mdm2 gene. Normally, MDM2 protein inhibits p53 function in an autoregulatory loop. Regulation of p53 by MDM2 is required for murine development as well as for proliferation of cultured human fibroblasts. However, E7-expressing human fibroblasts continue to divide even though E7 abrogates the ability of MDM2 and p53 to bind. Furthermore, E7-expressing cells are not more sensitive to UV light, an agent that has been reported to induce apoptosis mediated by p53. These results indicate that in addition to inhibiting the ability of MDM2 to regulate p53, E7 must block signaling steps downstream of p53 to allow cell division.

Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet light.

The mdm2 (murine double minute 2) oncogene encodes several proteins, the largest of which (p90) binds to and inactivates the p53 tumor suppressor protein. Multiple MDM2 proteins have been detected in tumors and in cell lines expressing high levels of mdm2 mRNAs. Here we show that one of these proteins (p76) is expressed, along with p90, in wild-type and p53-null mouse embryo fibroblasts, indicating that it may have an important physiological role in normal cells. Expression of this protein is induced, as is that of p90, by UV light in a p53-dependent manner. The p76 protein is synthesized via translational initiation at AUG codon 50 and thus lacks the N terminus of p90 and does not bind p53. In cells, p90 and p76 can be synthesized from mdm2 mRNAs transcribed from both the P1 (constitutive) and P2 (p53-responsive) promoters. Site-directed mutagenesis reveals that these RNAs give rise to p76 via internal initiation of translation. In addition, mdm2 mRNAs lacking exon 3 give rise to p76 exclusively, and such mRNAs are induced by p53 in response to UV light. These data indicate that p76 may be an important product of the mdm2 gene and a downstream effector of p53.

Regulation of transcriptional activation of mdm2 gene by p53 in response to UV radiation.

The mdm2 oncogene is expressed at elevated levels in a variety of human tumors, and its product inactivates the p53 tumor suppressor protein. MDM2 forms an autoregulatory loop with p53, because the mdm2 gene contains a promoter that is responsive to p53. Synthesis of MDM2 protein increases in a p53-dependent manner in response to DNA-damaging agents such as UV light. Although this increase likely results from enhanced transcription, the amount of MDM2 protein does not correspond to the amount of p53 protein in cells exposed to UV light. Here we show that the p53-specific internal promoter in the mdm2 gene is induced after exposure to UV light, whereas the upstream constitutive promoter is not induced. The amount of the mdm2 transcript does not parallel the ability of p53 to bind DNA, indicating that transcription is regulated at a step distinct from activation of the DNA-binding function of p53.

Delineation of additional genetic bases for C8 beta deficiency. Prevalence of null alleles and predominance of C-->T transition in their genesis.

We studied the molecular bases for C8 beta deficiency in 34 unrelated families from the United States and the former Soviet Union. These families represented 69 unrelated null alleles of which 59 (86%) were found to be due to a previously described C-->T transition in exon 9. Six additional null alleles were also caused by C-->T transitions, of which four (6%) were located at base 388 in exon 3, one (2%) at base 298 in exon 3, and one (2%) involved cytosine 847 in exon 6. All of the null alleles affecting cytosine 388 were linked to the sequence polymorphism at base 376, which determines the uncommon C8 beta acidic allotype. Two null alleles were caused by single base pair deletions of cytosines at positions 430 and 632 in exons 3 and 5, respectively. Of the characterized null alleles, 97% were due to C-->T transitions in which an arginine (64 alleles) or a glutamine (one allele) was replaced by a stop codon. The basis for this apparent high frequency of C-->T transitions occurring in a relatively short stretch of DNA is uncertain.

[Neonatal meningitis: observations on its etiology, mortality and sequelae]. / Meningitis neonatal: observaciones sobre etiología, mortalidad y secuelas.

A retrospective study was carried out on all cases diagnosed with neonatal meningitis at the Hospital Infantil de México Federico Gómez. A rate of 9.6 cases per 1,000 discharged patients was found as well as 6.7% association with sepsis. In 50 of the cases analyzed, an etiologic agent was identified in 23 children; the main bacteria identified were Escherichia coli (24%), Klebsiella pneumoniae (14%), Enterobacter (4%), Proteus mirabilis and Pseudomonas sp (2%), respectively. The mortality rate was 60% and sequelae were seen in 13 of the surviving 20 patients. The unfavorable prognosis of neonates with meningitis forces us to establish an early diagnosis, make every effort to identify the causing agent and try new medications as well as co-adjuvant treatments.

[Neonatal septicemia: differences in full-term and pre-term newborn infants]. / Septicemia neonatal: diferencias entre recién nacidos a término y de pretérmino.

Neonatal septicemia was assessed by blood cultures in 115 newborns (NB) during a two years study in a pediatric hospital of reference in Mexico City. The studied patients were divided in two groups of gestational age, and the differences of etiologic agents, clinical signs, laboratory findings and clinical outcome were compared at term and preterm neonates. We observed Staphylococcus epidermidis became the first cause of septicemia in at term NB (P less than 0.001), while Escherichia coli and Klebsiella pneumoniae (P less than 0.01) were more frequent in the preterm neonates. The clinical manifestations of fever (P less than 0.001), hepatomegaly (P less than 0.01), splenomegaly (P less than 0.05), and rejection to feeding (P less than 0.05) were more common in at term NB. On the other hand, apneas (P less than 0.01), hypothermia (P less than 0.02), and abdominal distension (P less than 0.05) were more frequent in the preterm NB. The altered white blood cell counts were more commonly observed in the preterm group, as leukopenia (P less than 0.05), neutropenia (P less than 0.01), and high I/T ratio (P less than 0.05). There were not significant differences in complications or sequels between the two groups; however, the mortality ratio was higher in the preterm NB group (P less than 0.02). Changing etiology of neonatal septicemia is discussed, and we propose these kind of data are very useful for purpose of detection, diagnostic and treatment of septic neonates.

Principales manifestaciones gastrointestinales de la giardiasis en ninos. / Main gastrointestinal manifestations of giardiasis in children

Se estudiaron 40 ninos con giardiasis con la finalidad de ver las principales manifestaciones gastrointestinales. Las manifestaciones mas frecuentemente encontradas fueron, diarrea cronica, detencion del crecimiento y dolor abdominal. La curva de absorcion a la lactosa fue anormal en la mayoria de los casos (0.71) en tanto que la absorcion de la D-Xilosa fue anormal en 0,40 de los casos. La biopsia intestinal fue normal en 0.51. La atrofia total de vellosidades se presento en 0.07 en tanto que la atrofia parcial se presento en 0.30. La asociacion bacteriana mas frecuente fue con Salmonella. La presencia de duodenitis (documentada radiologicamente) se encontro en 0.035, en tanto que la hiperplasia nodular linfoide (colon por enema con doble contraste) se encontro en 0.38. En la mayoria de los ninos con dolor abdominal se encontro una buena correlacion entre esta manifestacion y la intolerancia a la lactosa

Morbilidad perinatal en el desprendimiento prematuro de placenta. / Perinatal mortality in abruptio placentae

En 91 casos de desprendimiento prematuro de placenta estudiados, se encontro que la incidencia de la mortalidad perinatal es de 65.93 por ciento, porcentaje del que la mayor parte (51.65 por ciento) corresponde a muertes fetales. Hubo 14.28 por ciento de mortalidad neonatal , siendo las causas principales de muerte la insuficiencia respiratoria y las grandes malformaciones congenitas incompatibles con la vida. La mayoria de los ninos estudiados fueron prematuros (peso de 1.001 a 2.500 g y gestacion de 29 a 36 semanas) por lo que no llamo la atencion ver el gran indice de problemas respiratorios encontrados, sobre todo por la adicion del factor hipoxia a la condicion organica de prematurez. Se concluye que el mejor control de las pacientes durante el embarazo y el trabajo de parto, asi como la oportuna resolucion del mismo por via abdominal y la atencion pediatrica integral, pueden reducir notablemente el porcentaje correspondiente a mortalidad perinatal

[The potentially infected newborn infant]. / El recién nacido potencialmente infectado.

In order to establish relationship between premature rupture of membranes (RPM) and neonatal infection, together with the importance of other factors during this process, 50 newborns with history of RPM were studied. In a control group and in groups of newborns with less than and more than 24 hours of plain RPM, related to clinically healthy and vigorous infants, no case of infection was found. On the other hand, 30% and 60% respectively of infections were found in groups less than and more than 24 hours of RPM, but with the presence of other contaminating factors that impair immunological response of the newborn, such as: acute maternal infection, prolonged delivery, unexpected birth, pediatric reanimation procedures, organic immaturity, fetal suffering, immediatie neonatal depression and intercurrent pathology. There were two deaths: a case with RPM of 5 hours and another one with 38 hours, but both with high rating due to the presence and intensity of "aggravating factors" mentioned having internal action mechanism that apparently of restrains to the perpetuation of the hypoxia-acidosis cycle. A provisional sheet is presented to evaluate such "aggravating factors" considering that an RPM associated to them represents a high risk of neonatal infection. In cases of clinically healthy newborns with plain RPM, we advice only to watch over them for 3--5 day, but no antimicrobial treatment at all.