Entrapment of the Volar Plate in the Retrocondylar Space of the Proximal Interphalangeal Joint Necessitating Open Reduction and Internal Fixation: A Case Report.

Introduction: Fracture-dislocations of the proximal interphalangeal joint (PIPJ) can have a significant impact on digital motion and hand function if inappropriately treated. While these injuries are commonly encountered, they can be quite challenging to manage. It is critical to ensure a concentric reduction and early motion when treating these injuries. Case Report: A 17-year-old woman sustained a fracture-dislocation of the PIPJ of the left small finger. Despite a concentric closed reduction, she had pain and a mechanical block to PIPJ motion. Advanced imaging revealed volar plate entrapment in the retrocondylar space. She was treated with open reduction and direct volar plate repair. Postoperatively, the patient had an excellent outcome with no complications. Conclusion: Our case highlights the importance of both performing an anesthetized examination and investigating the etiology of any limitations to motion even if there is an initial acceptable closed reduction.

Dorsal Approach for Management of Proximal Interphalangeal Joint Flexion Contracture.

Proximal interphalangeal (PIP) joint contracture is a common, difficult clinical problem that can arise from minor trauma. Management is difficult because outcomes are unpredictable and often poor, due to residual flexion deformities postoperatively. The dorsal approach for flexion contracture of the PIP joint is not discussed in present literature. In this technique guide, we wish to describe and explain the rationale for a dorsal approach. In our experience, a dorsal approach allows for ease of access to all pathologic structures, with simple positioning of the digit to allow access to volar structures, as well as when addressing more than one digits with a PIP contracture. Finally, similar to the midaxial approach, the dorsal approach also eliminates any volar soft tissue concerns and need for supplemental coverage.

HIV-1 Gag specificity for PIP2 is regulated by macromolecular electric properties of both protein and membrane local environments.

HIV-1 assembly occurs at the plasma membrane, with the Gag polyprotein playing a crucial role. Gag association with the membrane is directed by the matrix domain (MA), which is myristoylated and has a highly basic region that interacts with anionic lipids. Several pieces of evidence suggest that the presence of phosphatidylinositol-(4,5)-bisphosphate (PIP2) highly influences this binding. Furthermore, MA also interacts with nucleic acids, which is proposed to be important for the specificity of GAG for PIP2-containing membranes. It is hypothesized that RNA has a chaperone function by interacting with the MA domain, preventing Gag from associating with unspecific lipid interfaces. Here, we study the interaction of MA with monolayer and bilayer membrane systems, focusing on the specificity for PIP2 and on the possible effects of a Gag N-terminal peptide on impairing the binding for either RNA or membrane. We found that RNA decreases the kinetics of the protein association with lipid monolayers but has no effect on the selectivity for PIP2. Interestingly, for bilayer systems, this selectivity increases in presence of both the peptide and RNA, even for highly negatively charged compositions, where MA alone does not discriminate between membranes with or without PIP2. Therefore, we propose that the specificity of MA for PIP2-containing membranes might be related to the electrostatic properties of both membrane and protein local environments, rather than a simple difference in molecular affinities. This scenario provides a new understanding of the regulation mechanism, with a macromolecular view, rather than considering molecular interactions within a ligand-receptor model.

Regulation of ThermoTRP Channels by PIP2 and Cholesterol.

Transient receptor potential (TRP) ion channels are proteins that are expressed by diverse tissues and that play pivotal functions in physiology. These channels are polymodal and are activated by several stimuli. Among TRPs, some members of this family of channels respond to changes in ambient temperature and are known as thermoTRPs. These proteins respond to heat or cold in the noxious range and some of them to temperatures considered innocuous, as well as to mechanical, osmotic, and/or chemical stimuli. In addition to this already complex ability to respond to different signals, the activity of these ion channels can be fine-tuned by lipids. Two lipids well known to modulate ion channel activity are phosphatidylinositol 4,5-bisphosphate (PIP2) and cholesterol. These lipids can either influence the function of these proteins through direct interaction by binding to a site in the structure of the ion channel or through indirect mechanisms, which can include modifying membrane properties, such as curvature and rigidity, by regulating their expression or by modulating the actions of other molecules or signaling pathways that affect the physiology of ion channels. Here, we summarize the key aspects of the regulation of thermoTRP channels by PIP2 and cholesterol.

PIP4K2A and PIP4K2C transcript levels are associated with cytogenetic risk and survival outcomes in acute myeloid leukemia.

Phosphoinositide signaling pathway orchestrates primordial molecular and cellular functions in both healthy and pathologic conditions. Phosphatidylinositol-5-phosphate 4-kinase type 2 lipid kinase (PIP4K2) family, which compromises PIP4K2A, PIP4K2B and PIP4K2C, has drawn the attention in human cancers. Particularly in hematological malignancies, PIP4K2A was already described as an essential protein for a malignant phenotype, although the clinical and biological impact of PIP4K2B and PIP4K2C proteins have not being explored in the same extent. In the present study, we investigated the impact on clinical outcomes and gene network of PIP4K2A, PIP4K2B and PIP4K2C mRNA transcripts in acute myeloid leukemia (AML) patients included in The Cancer Genome Atlas (2013) study. Our results indicate that PIP4K2A and PIP4K2C, but not PIP4K2B, mRNA levels were significantly reduced in AML patients assigned to the favorable risk group (p < 0.05) and low levels of PIP4K2A and PIP4K2C positively affect clinical outcomes of AML patients (p < 0.05). Gene set enrichment analyses indicate that the expression of PIP4K2 genes is associated with biological process such as signal transduction, metabolism of RNA and genomic instability related-gene sets. In summary, our study provides additional evidence of the involvement of members of the PIP4K2 family, in particular PIP4K2A and PIP4K2C, in AML.

Cytoskeleton disruption affects Kv2.1 channel function and its modulation by PIP2.

Voltage-gated potassium channels are expressed in a wide variety of excitable and non-excitable cells and regulate numerous cellular functions. The activity of ion channels can be modulated by direct interaction or/and functional coupling with other proteins including auxiliary subunits, scaffold proteins and the cytoskeleton. Here, we evaluated the influence of the actin-based cytoskeleton on the Kv2.1 channel using pharmacological and electrophysiological methods. We found that disruption of the actin-based cytoskeleton by latrunculin B resulted in the regulation of the Kv2.1 inactivation mechanism; it shifted the voltage of half-maximal inactivation toward negative potentials by approximately 15 mV, accelerated the rate of closed-state inactivation, and delayed the recovery rate from inactivation. The actin cytoskeleton stabilizing agent phalloidin prevented the hyperpolarizing shift in the half-maximal inactivation potential when co-applied with latrunculin B. Additionally, PIP2 depletion (a strategy that regulates Kv2.1 inactivation) after cytoskeleton disruption does not regulate further the inactivation of Kv2.1, which suggests that both factors could be regulating the Kv2.1 channel by a common mechanism. In summary, our results suggest a role for the actin-based cytoskeleton in regulating Kv2.1 channels.

Plant Aquaporins: Diversity, Evolution and Biotechnological Applications.

The plasma membrane forms a permeable barrier that separates the cytoplasm from the external environment, defining the physical and chemical limits in each cell in all organisms. The movement of molecules and ions into and out of cells is controlled by the plasma membrane as a critical process for cell stability and survival, maintaining essential differences between the composition of the extracellular fluid and the cytosol. In this process aquaporins (AQPs) figure as important actors, comprising highly conserved membrane proteins that carry water, glycerol and other hydrophilic molecules through biomembranes, including the cell wall and membranes of cytoplasmic organelles. While mammals have 15 types of AQPs described so far (displaying 18 paralogs), a single plant species can present more than 120 isoforms, providing transport of different types of solutes. Such aquaporins may be present in the whole plant or can be associated with different tissues or situations, including biotic and especially abiotic stresses, such as drought, salinity or tolerance to soils rich in heavy metals, for instance. The present review addresses several aspects of plant aquaporins, from their structure, classification, and function, to in silico methodologies for their analysis and identification in transcriptomes and genomes. Aspects of evolution and diversification of AQPs (with a focus on plants) are approached for the first time with the aid of the LCA (Last Common Ancestor) analysis. Finally, the main practical applications involving the use of AQPs are discussed, including patents and future perspectives involving this important protein family.

Regulation of thermoTRPs by lipids.

The family of Transient Receptor Potential (TRP) ion channels is constituted by 7 subfamilies among which are those that respond to temperature, the thermoTRPs. These channels are versatile molecules of a polymodal nature that have been shown to be modulated in various fashions by molecules of a lipidic nature. Some of these molecules interact directly with the channels on specific regions of their structures and some of these promote changes in membrane fluidity or modify their gating properties in response to their agonists. Here, we have discussed how some of these lipids regulate the activity of thermoTRPs and included some of the available evidence for the molecular mechanisms underlying their effects on these channels.

Phosphatidylinositol 4-phosphate 5-kinases 1 and 2 are involved in the regulation of vacuole morphology during Arabidopsis thaliana pollen development.

The pollen grains arise after meiosis of pollen mother cells within the anthers. A series of complex structural changes follows, generating mature pollen grains capable of performing the double fertilization of the female megasporophyte. Several signaling molecules, including hormones and lipids, have been involved in the regulation and appropriate control of pollen development. Phosphatidylinositol 4-phophate 5-kinases (PIP5K), which catalyze the biosynthesis of the phosphoinositide PtdIns(4,5)P2, are important for tip polar growth of root hairs and pollen tubes, embryo development, vegetative plant growth, and responses to the environment. Here, we report a role of PIP5Ks during microgametogenesis. PIP5K1 and PIP5K2 are expressed during early stages of pollen development and their transcriptional activity respond to auxin in pollen grains. Early male gametophytic lethality to certain grade was observed in both pip5k1(-/-) and pip5k2(-/-) single mutants. The number of pip5k mutant alleles is directly related to the frequency of aborted pollen grains suggesting the two genes are involved in the same function. Indeed PIP5K1 and PIP5K2 are functionally redundant since homozygous double mutants did not render viable pollen grains. The loss of function of PIP5K1 and PIP5K2results in defects in vacuole morphology in pollen at the later stages and epidermal root cells. Our results show that PIP5K1, PIP5K2 and phosphoinositide signaling are important cues for early developmental stages and vacuole formation during microgametogenesis.

Early LPS-induced ERK activation in retinal pigment epithelium cells is dependent on PIP 2 -PLC.

This article presents additional data regarding the study "The phospholipase D pathway mediates the inflammatory response of the retinal pigment epithelium" [1]. The new data presented here show that short exposure of RPE cells to lipopolysaccharide (LPS) induces an early and transient activation of the extracellular signal-regulated kinase (ERK1/2). This early ERK1/2 activation is dependent on phosphatidylinositol bisphosphate-phospholipase C (PIP2-PLC). On the contrary, neither the phospholipase D 1 (PLD1) nor the PLD2 inhibition is able to modulate the early ERK1/2 activation induced by LPS in RPE cells.

ARID5B, CEBPE and PIP4K2A Germline Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia in Mexican Patients: A MIGICCL Study.

BACKGROUND AND AIMS: Childhood acute lymphoblastic leukemia (ALL) is the leading cause of childhood cancer-related deaths worldwide. Multiples studies have shown that ALL seems to be originated by an interaction between environmental and genetic susceptibility factors. The ARID5B polymorphisms are among the most reproducible ALL associated-risk alleles in different populations. The aim of the present study was to examine the contribution of ARID5B, CEBPE, and PIP4K2 risk alleles for the development of ALL in children from Mexico City and Yucatan, Mexico. METHODS: A study was conducted with a total of 761 unrelated subjects. Two hundred eighty five ALL cases (111 from Yucatan and 174 from Mexico City) and 476 healthy subjects. Genotyping included the rs7088318 (PIP4K2A), rs10821936 (ARID5B), rs7089424 (ARID5B) and rs2239633 (CEBPE) polymorphisms. RESULTS: Associations between ALL and rs10821936 and rs7089424 ARID5B SNPs were found (OR = 1.9, 95% CI (1.5-2.4) and OR = 2.0, 95% CI (1.6-2.5), respectively). Moreover, a higher risk was observed in the homozygous risk genotypes of carriers from Mexico City (OR = 3.1, 95% CI (2.0-4.9) and OR 3.1, CI 95% (2.0-4.8), respectively). Otherwise, the rs7088318 (PIP4K2A) and rs2239633 (CEBPE) polymorphisms were not associated with ALL risk. CONCLUSIONS: Our analysis suggests that ARID5B confers risk for childhood ALL in a Mexican population.

Differential profile of PIP4K2A expression in hematological malignancies.

PIP4K2A is a lipid kinase that phosphorylates PtdIns5P, generating PtdIns4,5P2. Recently, PIP4K2A was identified as a potential target in acute myeloid leukemia cells. The objective of the present study was to investigate the PIP4K2A expression in hematological malignancies and verify the effects of PIP4K2A silencing on proliferation and survival of leukemia cell lines. PIP4K2A was found to be a cytoplasmic and nuclear protein with reduced levels in leukemia cell lines compared to normal leukocytes. PIP4K2A mRNA levels were significantly reduced in bone marrow cells from acute lymphoid leukemia (ALL) patients compared with healthy donors and in myelodysplastic syndromes (MDS) with ≥5% compared with <5% bone marrow blasts. Low PIP4K2A expression (lowest tertile versus 2 higher tertiles) negatively impacted overall survival of MDS patients by univariate analysis. PIP4K2A silencing did not modulate cell proliferation, clonogenicity and apoptosis of HEL and Namalwa leukemia cells. In summary, we characterized the expression of PIP4K2A in a cohort of patients with hematological malignancies and we found that PIP4K2A mRNA expression is downregulated in RAEB-1/RAEB-2 MDS and ALL cells, and PIP4K2A silencing does not modulate cell survival in HEL and Namalwa leukemia cells.

Resultados de un programa de seguimiento de las prótesis mamarias pip (poly-implant-prothese) / Results of a program to monitor the pip breast prostheses (poly-implant-prothese)

Objective: The rupture of mammary protheses PIP (poly-implant-prothese) caused an alarm, settling in Spain a protocol for the management of patients. As hospital unit of reference for the management, monitoring and treatment of patients carrying PIP breast implants, we propose objective to make a descriptive study of the current situation in our country and compare it to the hitherto described in the literature. Method: We conducted a transversal study of all patients who came during the years 2012 and 2013, to the Unit of Mammary Pathology of the Universitary General Hospital of Elche. Results: With a total of 285 women, we observed a high rate of implant rupture (50.2 percent) asymptomatic most (84.6 percent). Fact that the year 2006 had the highest percentage of breakage and the appearance of siliconomas. Conclusions: Our series confirms rupture rate similar to that described in the literature for PIP breast implants. We observed a higher percentage of breakage from the year 2006, coinciding with the period of manufacture described poorer quality of these implants. Axillary siliconomas were evident in 35.1 percent of patients, the only locally axillary symptoms.

Objetivo: La rotura de las prótesis mamarias PIP (poly-implant-prothese) ha supuesto una alarma, estableciéndose en España un protocolo para el manejo y seguimiento de las pacientes. Como unidad hospitalaria de referencia para el manejo, seguimiento y tratamiento de las pacientes portadoras de prótesis mamarias PIP, nos proponemos como objetivo realizar un estudio descriptivo de la situación actual en nuestro medio y compararlo con lo hasta ahora descrito en la literatura. Método: Realizamos un estudio transversal de todas las pacientes que acudieron durante los años 2012 y 2013, a la Consulta de la Unidad de Patología Mamaria del Hospital General Universitario de Elche. Resultados: Con un total de 285 mujeres, observamos la elevada tasa de ruptura de los implantes (50,2 por ciento) la mayoría asintomáticos (84,6 por ciento). Siendo el año 2006 el de mayor porcentaje de rotura y la aparición de siliconomas. Conclusiones: Se confirma una tasa de ruptura similar a la descrita en la literatura para los implantes mamarios PIP. Observamos un mayor porcentaje de rotura a partir del año 2006, coincidiendo con el período de fabricación descrito de peor calidad de estos implantes. Se evidenciaron siliconomas axilares en el 35,1 por ciento de las pacientes, siendo la única sintomatología a nivel local axilar.

A structural view of ligand-dependent activation in thermoTRP channels.

Transient Receptor Potential (TRP) proteins are a large family of ion channels, grouped into seven sub-families. Although great advances have been made regarding the activation and modulation of TRP channel activity, detailed molecular mechanisms governing TRP channel gating are still needed. Sensitive to electric, chemical, mechanical, and thermal cues, TRP channels are tightly associated with the detection and integration of sensory input, emerging as a model to study the polymodal activation of ion channel proteins. Among TRP channels, the temperature-activated kind constitute a subgroup by itself, formed by Vanilloid receptors 1-4, Melastatin receptors 2, 4, 5, and 8, TRPC5, and TRPA1. Some of the so-called "thermoTRP" channels participate in the detection of noxious stimuli making them an interesting pharmacological target for the treatment of pain. However, the poor specificity of the compounds available in the market represents an important obstacle to overcome. Understanding the molecular mechanics underlying ligand-dependent modulation of TRP channels may help with the rational design of novel synthetic analgesics. The present review focuses on the structural basis of ligand-dependent activation of TRPV1 and TRPM8 channels. Special attention is drawn to the dissection of ligand-binding sites within TRPV1, PIP2-dependent modulation of TRP channels, and the structure of natural and synthetic ligands.

Prospective study of hammertoe correction with an intramedullary implant.

BACKGROUND: Operative correction of a hammertoe deformity is often accomplished by excision of the articular surface of the proximal interphalangeal joint (PIP) and fixation across the joint. This study aimed to prospectively evaluate clinical and radiographic outcomes of hammertoe operative correction utilizing an internal implant and assess its ability to maintain postoperative alignment. METHODS: Twenty-nine patients (53 toes) with a painful rigid hammertoe deformity were prospectively enrolled and operatively treated with resection arthroplasty of the PIP joint and fixation with an implant. Five patients were lost to follow-up, and 24 patients (42 toes) returned at an average of 12 months for final clinical and radiographic evaluation. All patients were evaluated pre- and postoperatively by AOFAS and Visual Analog Pain Scale (VAS) scores. On physical exam, the location and magnitude of the deformity, callosities, and digit circumference were recorded. Radiological parameters evaluated were digital alignment, successful union, implant position, and bone reaction. RESULTS: All patients reported satisfaction at final follow-up, with an average improvement of AOFAS score from 52 (range, 24-87 points) to 71 (range, 42-95 points) points. The mean VAS pain score improved from 5 points (range, 2 to 10) preoperatively to 1 point (range, 0 to 5) postoperatively. Of patients, 87% reported an ability to return to their preoperative activities without limitations. Regarding digital alignment, there were no recurrent deformities or transverse plane deformities; 1 toe presented with a minor digital rotational deformity at final follow-up. Postoperative radiographs indicated 100% of proximal interphalangeal (PIP) joints with good alignment, and 81% demonstrated bony union. CONCLUSION: Our results suggest that utilization of an internal implant for hammertoe correction was safe and provided acceptable alignment, pain reduction, and improved function at final follow-up. LEVEL OF EVIDENCE: Level IV, case series.