Bibliometric Analysis of Ophthalmology Publications from Arab Countries between 2012 and 2022.

PURPOSE: The purpose of this study was to conduct a bibliometric analysis of articles published in Ophthalmology Journals from Arab countries from 2012 to 2022. METHODS: This cross-sectional analysis of all original ophthalmology research and review articles published by authors with an affiliation with an institution from Arab countries and indexed in the ISI Web of Science between January 2012 and December 2022. RESULTS: For the years 2012-2022, 4292 articles published in Ophthalmology Journals by authors from Arab-based institutions were identified. A 2.11-fold progressive increase in the number of publications was observed over the last decade with a substantial increase in publication volume during the first 2 years of the COVID-19 pandemic. The countries with the highest number of publications were Egypt (38.51%), Saudi Arabia (35.56%), and the United Arab Emirates (7.88%). According to affiliation, authors from King Khaled Eye Specialist Hospital (KKESH) (n = 644) published the highest number of ophthalmology articles, followed by King Saud University (n = 585) and Cairo University (n = 393). CONCLUSION: Over the last decade, the overall productivity of research in the field of ophthalmology has significantly increased. Majority of the articles in ophthalmology were published by authors from Egypt and Saudi Arabia with KKESH as the most productive institution among Arab nations.

Changes in Stage Distribution and Disease-Specific Survival in Differentiated Thyroid Cancer with Transition to American Joint Committee on Cancer 8th Edition: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent revision significantly changed the American Joint Committee on Cancer (AJCC) staging criteria for differentiated thyroid cancer (DTC). To quantitatively evaluate resulting changes in patient stage distribution and the associated disease-specific survival (DSS) incorporating diverse populations, we performed a meta-analysis of studies comparing the AJCC 7th edition (AJCC-7) with 8th edition (AJCC-8) staging for DTC. MATERIALS AND METHODS: After PROSPERO registration (#CRD42019123657), publications in English reporting DSS of DTC with AJCC-7 and AJCC-8 from inception to June 2019 were identified by search of MEDLINE and PubMed. Random-effects meta-analyses were conducted to compare differences in survival between AJCC-7 and AJCC-8. Pooled hazard ratios, 10-year DSS, and corresponding interval estimates were calculated for AJCC subgroups. Differences in survival between editions were assessed using subgroup analysis with nonoverlapping confidence intervals indicating statistical significance. RESULTS: Final analysis included six studies with 10,850 subjects and median follow-up from 55 to 148 months. Use of AJCC-8 shifted classification to earlier stages: stage I, from 60% to 81%; stage II, from 5% to 13%; stage III, from 21% to 2%; stage IV, from 10% to 3%. Ten-year DSS was significantly lower in AJCC-8 versus AJCC-7 in patients with stage II (88.6%, 95% confidence interval [CI] 82.7-94.6% vs. 98.1%, 95% CI 96.6-99.6%, respectively) and stage III disease (70.5%, 95% CI 59.1-83.9% vs. 96.8%, 95% CI 94.1-99.64%, respectively). CONCLUSION: Meta-analysis of revised AJCC staging for DTC, incorporating diverse populations, demonstrates redistribution of patients toward earlier clinical stages and better stratification of disease-specific mortality risk, specifically among patients now classified with stage II and III disease. IMPLICATIONS FOR PRACTICE: This study provides updated estimates of disease-specific survival for patients with differentiated thyroid cancer determined by the American Joint Committee on Cancer staging system that are generalizable to broader populations and support improved stratification using the recently revised criteria.

Maternal diabetes: A potential risk factor of congenital hearing loss

@#Objective. The purpose of this study is to identify the incidence rate of 'refer' result in neonates born to diabetic mothers and to determine the association of maternal diabetes and the initial 'refer' result. Methods. This was a retrospective cross-sectional study which included neonates who had hearing screening test using transient-evoked otoacoustic emissions test (TEOAE) on both ears at the Philippine General Hospital Ear unit during three weeks. We obtained the demographic characteristics, presence/absence of maternal diabetes, and OAE results. Results. Among the 150 neonates, ten were born to diabetic mothers, with an age range of 2-8 days old. Forty percent of neonates of diabetic mothers had an initial 'refer' result compared with 7.9% of nondiabetic mothers' neonates. After logistic regression analysis, there is a significant association between maternal diabetes and initial 'refer' result in OAE with a p-value <0.05. If the mother is diagnosed with diabetes (gestational/pre-gestational), the odds of having an initial 'refer' result in the hearing screening is 2x higher. The odds can range from 2-43 times. Conclusion. The incidence rate of an initial 'refer' result in neonates of diabetic mothers is 40%. There is a significant association between maternal diabetes and the initial 'refer' result in the OAE test.

Head and neck symptoms as predictors of outcome in tetanus patients

@#Objective: This study aims to investigate which, if any head and neck symptoms (trismus, dysphagia, alterations in speech or facial movements, and dyspnea) might be good predictors of outcomes (mortality, tracheostomy, discharged, decannulated) and prognosis of tetanus patients. Methods: Design: Retrospective Cohort Study Setting: Tertiary National University Hospital Patients: Seventy-three (73) pediatric and adult patients diagnosed with tetanus and admitted at the emergency room of the Philippine General Hospital between January 1, 2013 and December 31, 2017. Demographic characteristics, incubation periods, periods of onset, routes of entry, head and neck symptoms, stage, and outcomes were retrieved from medical records and analyzed. Results: Of the 73 patients included, 53 (73%) were adults, while the remaining 20 (27%) were pediatric. The three most common head and neck symptoms were trismus (48; 66%), neck pain/ rigidity (35; 48%), and dysphagia to solids (31; 42%). Results of multivariate logistic regression analysis showed that only trismus (OR = 3.742, p = .015) and neck pain/ rigidity (OR = 4.135, p = .015) were significant predictors of decannulation. No dependent variable/symptoms had a significant effect in predicting discharge and mortality. Conclusion: Clinically diagnosed tetanus can be easily recognized and immediately treated. Most of the early complaints are head and neck symptoms that can help in early diagnosis and treatment resulting in better prognosis. In particular, trismus and neck pain/rigidity may predict the outcome of decannulation after early tracheotomy, but not of discharge and mortality.

Electron correlation effects in the photoionization of CO and isoelectronic diatomic molecules.

This paper investigates the first sigma satellite band, which is by far the most prominent, in the valence photoelectron spectra for a set of isoelectronic diatomic molecules: carbon monoxide, carbon monosulfide, carbon monoselenide, silicon monoxide and boron monofluoride. In particular, we analyze the effect of the electronic structure, with the change of the atomic pair along the row and column of the periodic table on the position of the satellite peak as well as on the related dynamical observables profiles. For this investigation, highly correlated calculations have been performed on the primary ionic states and the satellite band for all the molecules considered. Cross sections for the primary ionic states, calculated using Dyson orbitals, have been compared with those obtained with Hartree-Fock and Density Functional Theory to probe the impact of the correlation in the bound states on the photoionization observables. Limitations of a simple intensity borrowing mechanism clearly result from the analysis of the satellite state, characterized by different features with respect to the relevant primary states.

Lumbosacral spinal cord epidural stimulation improves voiding function after human spinal cord injury.

Deficits in urologic function after spinal cord injury (SCI) manifest both as a failure to store and empty, greatly impacting daily life. While current management strategies are necessary for urological maintenance, they oftentimes are associated with life-long side effects. Our objective was to investigate the efficacy of spinal cord epidural stimulation (scES) as a promising therapy to improve bladder control after SCI. A bladder mapping study was undertaken for sixteen sessions over the course of four months in an individual with chronic, motor complete SCI. Varying combinations of stimulating cathode electrodes were initially tested during filling cystometry resulting in the identification of an effective configuration for reflexive bladder emptying at the caudal end of the electrode array. Subsequent systematic testing of different frequencies at a fixed stimulus intensity and pulse width yielded lowest post-void residual volumes at 30 Hz. These stimulation parameters were then tested in four additional research participants and found to also improve reflexive voiding efficiency. Taken together with SCI studies on step, stand, voluntary motor control and cardiovascular regulation, these findings further corroborate that scES has an all-encompassing potential to increase the central state of excitability, allowing for the control of multiple body functions, including the urological system.

Mapping the influence of socioeconomic development plans on Philippine Health Research Agenda: A descriptive study

Background@#Understanding and addressing social determinants of health through evidence-based action is a strategy that has been advocated by the World Health Organization as part of its “Health for All” strategy in 1978 and “Health in All Policies“ framework in 2013. It has then been recommended that the research agenda-setting process should be informed by socio-economic development plans with the specific aim of gathering data on social, economic, and cultural conditions that affect health.@*Objective@#This paper reviewed the PDP 2011-2016, PDP 2017-2022, MDGs, and SDGs and identified common directions with the NUHRA 2011-2016 and 2017-2022.@*Methods@#A content analysis of the three identified priorities of the NUHRA vis-a-vis the PDP 2011-2016, the PDP 2017-2022, the MDGs, and the SDGs was done in order to identify harmonization of the priorities of the NUHRAs targets and indicators with those of the other plans and agendas. A gap analysis across all topics was done to identify links and gaps.@*Results@#The results established the common ground between health research priorities and international and national plans. Comparing the number of direct relationships between the NUHRAs, PDPs, MDGs, and SDGs, it was noted that there were more direct links between NUHRA 2017-2022, PDP 2017-2022, and the SDGs compared to NUHRA 2011-2016, PDP 2011-2016, and MDGs. The direct links were mostly found in 1) maternal, newborn and child health, 2) health systems, 3) communicable diseases, 4) water, sanitation, and hygiene, 5) environment, and 6) infrastructure development.@*Conclusion@#The NUHRAs may serve as pathways to achieve the goals stipulated in other socio-economic development plans. The relationships of these to health are complex, nonlinear and often the effects manifest after a long period of time, and as such require rigorous research.

Operationalizing the development of the National Unified Health Research Agenda 2017-2022

Introduction@#The National Unified Health Research Agenda is a major document whose creation by the Philippine National Health Research Systems is mandated by Philippine Law. Multiple frameworks, methods, and approaches for the development of a health research agenda exists. Available literature on research priority setting have mostly focused on its methods, results, or implementation. There are limited studies on the operations management of conducting a national health research priority-setting exercise.@*Objectives@#This paper aims to describe the operational components utilized to develop the NUHRA 2017-2022 and provide lessons learned for future research priority setting endeavors. @*Methods@#This paper identified and categorized the operational components to develop the NUHRA 2017-2022 using the Enabler Criterion of the European Foundation for Quality Management’s (EFQM) Excellence Model.@*Results@#Operationalizing the development of a national health research agenda requires the harmonization of multiple components. Having region-based staff involved in the production of a regional situational analysis improved its context and accuracy. The workload for each cluster team must be considered and anticipated by the management. Stakeholder engagement requires political, diplomatic, advocacy, marketing, management, and technical skills. The process requires building relationships with various institutions. In a largescale project, management processes must be in place to effectively track and monitor its progress.@*Conclusion@#Operations and management are usually a neglected area in research and development projects. In a bottoms-up research priority-setting approach, iteration and flexibility is needed which requires a lot of management skills and insight. Duration of the project, planning, resources available, and quality of outputs have a strong interconnected relationship.

Enabling greater private sector participation in health research in the Philippines

@#<p style="text-align: justify;"><strong>OBJECTIVE:</strong> This study reviewed the current health research and development environment in the Philippines with respect to the engagement between the public and private sectors. The overall objective was to identify the role of the private sector in health research and identify barriers and opportunities for successful public-private health research partnerships.</p><p style="text-align: justify;"><strong>METHODS:</strong>  Key informant interviews were conducted using a semi-structured interview tool. Secondary data such as annual reports and project funding documents from the Philippine Council for Health Research and Development were also analyzed.</p><p style="text-align: justify;"><strong>RESULTS:</strong> The roles of the private sector when engaging with the public sector for research and development were identified as generators, funders, and adopters of research. Information gathered showed that there were several institutional and practice barriers to the successful collaboration of the public and private sectors, however there were also lessons learned from the successes of cases such as the Axis-Knee System, Sambong, and Lagundi technologies.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> The collaboration and partnership of the public and private sectors can be mutually beneficial. Government initiative to increase the ease of collaboration with the private sector in health research was found to be a necessary step to stimulate a productive health research environment.</p>

Operationalizing the development of the National Unified Health Research Agenda 2017-2022

INTRODUCTION: The National Unified Health Research Agenda is a major document whose creation by the Philippine National Health Research Systems is mandated by Philippine Law. Multiple frameworks, methods, and approaches for the development of a health research agenda exists. Available literature on research priority setting have mostly focused on its methods, results, or implementation. There are limited studies on the operations management of conducting a national health research priority-setting exercise.OBJECTIVES: This paper aims to describe the operational components utilized to develop the NUHRA 2017-2022 and provide lessons learned for future research priority setting endeavors.METHODS: This paper identified and categorized the operational components to develop the NUHRA 2017-2022 using the Enabler Criterion of the European Foundation for Quality Management's (EFQM) Excellence Model.RESULTS: Operationalizing the development of a national health research agenda requires the harmonization of multiple components. Having region-based staff involved in the production of a regional situational analysis improved its context and accuracy. The workload for each cluster team must be considered and anticipated by the management. Stakeholder engagement requires political, diplomatic, advocacy, marketing, management, and technical skills. The process requires building relationships with various institutions. In a largescale project, management processes must be in place to effectively track and monitor its progress.CONCLUSION: Operations and management are usually a neglected area in research and development projects. In a bottoms-up research priority-setting approach, iteration and flexibility is needed which requires a lot of management skills and insight. Duration of the project, planning, resources available, and quality of outputs have a strong interconnected relationship.

Multilocus family-based association analysis of seven candidate polymorphisms with essential hypertension in an african-derived semi-isolated brazilian population.

Background. It has been widely suggested that analyses considering multilocus effects would be crucial to characterize the relationship between gene variability and essential hypertension (EH). Objective. To test for the presence of multilocus effects between/among seven polymorphisms (six genes) on blood pressure-related traits in African-derived semi-isolated Brazilian populations (quilombos). Methods. Analyses were carried out using a family-based design in a sample of 652 participants (97 families). Seven variants were investigated: ACE (rs1799752), AGT (rs669), ADD2 (rs3755351), NOS3 (rs1799983), GNB3 (rs5441 and rs5443), and GRK4 (rs1801058). Sensitivity analyses were further performed under a case-control design with unrelated participants only. Results. None of the investigated variants were associated individually with both systolic and diastolic BP levels (SBP and DBP, respectively) or EH (as a binary outcome). Multifactor dimensionality reduction-based techniques revealed a marginal association of the combined effect of both GNB3 variants on DBP levels in a family-based design (P = 0.040), whereas a putative NOS3-GRK4 interaction also in relation to DBP levels was observed in the case-control design only (P = 0.004). Conclusion. Our results provide limited support for the hypothesis of multilocus effects between/among the studied variants on blood pressure in quilombos. Further larger studies are needed to validate our findings.

Effects of chronic baclofen use on active movement in an individual with a spinal cord injury.

STUDY DESIGN: Case report. OBJECTIVES: To describe a case of chronic use of oral baclofen in a patient with spinal cord injury limiting lower extremity movements. SETTING: Frazier Rehab Institute, Louisville, Kentucky and University of Louisville. REPORT: A 24-year-old male with a C5 AIS-B spinal cord injury received a neurophysiological examination pre and post cessation of the use of oral baclofen. The initial results revealed no motor activity below the level of the lesion during reinforcement maneuvers or active movements. Following discontinuance of baclofen, motor activity was detected in upper and lower extremity muscles during some tasks. Locomotor patterns during stepping on a treadmill with body weight support did not reveal excessive overactivity of the lower extremity muscles. The patient was also able to perform squats independently at 35-40% body weight support when standing on a treadmill. CONCLUSION: Baclofen is typically prescribed for the management of spasticity in individuals with spinal cord injury. The interaction of reduced spasticity on functional tasks is not well understood, raising an important limitation of neurological exams and classifications done under heavy dosages of medication.

Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry.

Association studies between ADIPOR1 genetic variants and predisposition to type 2 diabetes (DM2) have provided contradictory results. We determined if two single nucleotide polymorphisms (SNP c.-8503G>A and SNP c.10225C>G) in regulatory regions of ADIPOR1 in 567 Brazilian individuals of European (EA; N = 443) or African (AfA; N = 124) ancestry from rural (quilombo remnants; N = 439) and urban (N = 567) areas. We detected a significant effect of ethnicity on the distribution of the allelic frequencies of both SNPs in these populations (EA: -8503A = 0.27; AfA: -8503A = 0.16; P = 0.001 and EA: 10225G = 0.35; AfA: 10225G = 0.51; P < 0.001). Neither of the polymorphisms were associated with DM2 in the case-control study in EA (SNP c.-8503G>A: DM2 group -8503A = 0.26; control group -8503A = 0.30; P = 0.14/SNP 10225C>G: DM2 group 10225G = 0.37; control group 10225G = 0.32; P = 0.40) and AfA populations (SNP c.-8503G>A: DM2 group -8503A = 0.16; control group -8503A = 0.15; P = 0.34/SNP 10225C>G: DM2 group 10225G = 0.51; control group 10225G = 0.52; P = 0.50). Similarly, none of the polymorphisms were associated with metabolic/anthropometric risk factors for DM2 in any of the three populations, except for HDL cholesterol, which was significantly higher in AfA heterozygotes (GC = 53.75 +/- 17.26 mg/dL) than in homozygotes. We conclude that ADIPOR1 polymorphisms are unlikely to be major risk factors for DM2 or for metabolic/anthropometric measurements that represent risk factors for DM2 in populations of European and African ancestries.

Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry

Association studies between ADIPOR1 genetic variants and predisposition to type 2 diabetes (DM2) have provided contradictory results. We determined if two single nucleotide polymorphisms (SNP c.-8503G>A and SNP c.10225C>G) in regulatory regions of ADIPOR1 in 567 Brazilian individuals of European (EA; N = 443) or African (AfA; N = 124) ancestry from rural (quilombo remnants; N = 439) and urban (N = 567) areas. We detected a significant effect of ethnicity on the distribution of the allelic frequencies of both SNPs in these populations (EA: -8503A = 0.27; AfA: -8503A = 0.16; P = 0.001 and EA: 10225G = 0.35; AfA: 10225G = 0.51; P < 0.001). Neither of the polymorphisms were associated with DM2 in the case-control study in EA (SNP c.-8503G>A: DM2 group -8503A = 0.26; control group -8503A = 0.30; P = 0.14/SNP 10225C>G: DM2 group 10225G = 0.37; control group 10225G = 0.32; P = 0.40) and AfA populations (SNP c.-8503G>A: DM2 group -8503A = 0.16; control group -8503A = 0.15; P = 0.34/SNP 10225C>G: DM2 group 10225G = 0.51; control group 10225G = 0.52; P = 0.50). Similarly, none of the polymorphisms were associated with metabolic/anthropometric risk factors for DM2 in any of the three populations, except for HDL cholesterol, which was significantly higher in AfA heterozygotes (GC = 53.75 ± 17.26 mg/dL) than in homozygotes. We conclude that ADIPOR1 polymorphisms are unlikely to be major risk factors for DM2 or for metabolic/anthropometric measurements that represent risk factors for DM2 in populations of European and African ancestries.

X-ray absorption and resonant Auger spectroscopy of O2 in the vicinity of the O 1s-->sigma* resonance: experiment and theory.

We report on an experimental and theoretical investigation of x-ray absorption and resonant Auger electron spectra of gas phase O(2) recorded in the vicinity of the O 1s-->sigma(*) excitation region. Our investigation shows that core excitation takes place in a region with multiple crossings of potential energy curves of the excited states. We find a complete breakdown of the diabatic picture for this part of the x-ray absorption spectrum, which allows us to assign an hitherto unexplained fine structure in this spectral region. The experimental Auger data reveal an extended vibrational progression, for the outermost singly ionized X (2)Pi(g) final state, which exhibits strong changes in spectral shape within a short range of photon energy detuning (0 eV>Omega>-0.7 eV). To explain the experimental resonant Auger electron spectra, we use a mixed adiabatic/diabatic picture selecting crossing points according to the strength of the electronic coupling. Reasonable agreement is found between experiment and theory even though the nonadiabatic couplings are neglected. The resonant Auger electron scattering, which is essentially due to decay from dissociative core-excited states, is accompanied by strong lifetime-vibrational and intermediate electronic state interferences as well as an interference with the direct photoionization channel. The overall agreement between the experimental Auger spectra and the calculated spectra supports the mixed diabatic/adiabatic picture.

FORTRAN interface for code interoperability in quantum chemistry: the Q5Cost library.

Ab initio quantum-chemistry programs produce and use large amounts of data, which are usually stored on disk in the form of binary files. A FORTRAN library, named Q5Cost, has been designed and implemented in order to allow the storage of these data sets in a special data format built with the HDF5 technology. This data format allows the data to be represented as tree structures and is portable between different platforms and operating systems, making code interoperability and communication much easier. The libraries have been used to build many interfaces among different quantum chemistry codes, and the first scientific applications have been realized. This activity was carried out within the COST in Chemistry D23 project "MetaChem", in the Working Group "A meta-laboratory for code integration in ab initio methods".

Constant-atomic-final-state filtering of dissociative states in the O1s-->sigma* core excitation in O2.

The below-threshold region in core-excited O2 is very complex, consisting of a multitude of exchange-split states with mixed molecular orbital-Rydberg character. We have investigated the nature of these intermediate states by resonant Auger spectroscopy. In particular, we have obtained constant-atomic-final-state yield curves for several atomic peaks in the electron decay spectra which are stemming from ultrafast dissociation. The relative intensity of Auger decay leading to atomic final states is considered a signature of the relative weight of the sigma* character. This method allows one to "filter out" intermediate states with dissociative character. Extensive calculations have been performed by multi-reference configuration interaction at different interatomic distances in order to evaluate the potential curves of the core-excited states and propose a qualitative description of the dissociative molecular dynamics. The calculations show that the core-excited states have a relevant admixture of excitations to orbitals with Rydberg character and excitations to the sigma* orbital with different spin couplings. A diabatization of the adiabatic potential curves shows that the coupling between Rydberg and sigma* diabatic states is very different at the different crossing points and ultrafast dissociation occurs more easily on the lowest sigma* diabatic potential curve. As a consequence, the observation of atomic peaks only in the lower-energy region of the absorption curve is well justified.

Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis.

Cytogenetic and fluorescence in situ hybridization studies were successfully performed in 217 chronic lymphocytic leukemia (CLL). In all, 13 patients with 6q21 deletion were identified and characterized in comparison with 92 patients with 'favourable' karyotype (normal or 13q-), 69 cases with 'intermediate risk' (1-2 anomalies) and 43 cases with 'unfavourable' karyotype (complex, 11q- or 17p-). Six out of 13 cases with 6q- showed an excess of atypical lymphocytes, a finding confirmed at the histologic level; >20% CD38+ cells were seen in 5/6 cases. IGVH mutational status revealed >98% homology to the germline sequence in 4/10 cases. When compared with the 'favourable' group, patients with 6q- showed a higher white blood cell (WBC) count, frequent splenomegaly, atypical morphology, CD38+ and short time from diagnosis to first treatment and short survival. A higher median WBC count was found in the 6q- group vs the intermediate-risk group; survival was shorter in the unfavourable group. To ascertain if the 6q- anomaly was an independent factor predicting for an inferior outcome among those patients with 'favourable' cytogenetics, we performed an analysis of prognostic factors in 105 patients (92 'favourable' plus 13 with 6q-), showing that the 6q- chromosome maintained its prognostic significance at multivariate analysis (P=0.02) along with stage (P=0.01). We conclude that CLL with 6q- is characterized by a high incidence of atypical morphology, classical immunophenotype with CD38 positivity and intermediate incidence of IGVH somatic hypermutation. Clinicobiological features and outcome show that this cytogenetic subset of CLL should be allocated in an intermediate-risk category.

O 1s --> sigma* resonance in O2: inadequacy of only two exchange-split components.

The O 1s-->sigma* transition below the O K-edge in O2 has been investigated by absorption, constant ionic state (CIS) experiments, and extensive configuration interaction calculations. CIS scans of the three lowest-lying final states reached in resonant Auger decay provide a wealth of information on energy range, symmetry, and spin multiplicity of the intermediate states with sigma* character. We conclude that the identification of only two exchange-split components is inadequate because a complex manifold of states with sigma* character exists with no unique energy difference between related states.

Preferential expression of the transcription coactivator HTIF1alpha gene in acute myeloid leukemia and MDS-related AML.

HTIF1alpha, a transcription coactivator which is able to mediate RARalpha activity and functionally interact with PML, is encoded by a gene on chromosome 7q32-34, which is a critical region in acute myeloid leukemias (AML). With the assumption that this gene may be related to AML, we investigated the HTIF1alpha DNA structure and RNA expression in leukemic cells from 36 M1-M5 AML patients (28 "de novo" and eight "secondary" to myelodysplastic syndrome (MDS)). Abnormal HTIF1alpha DNA fragments were never found, whereas loss of HTIF1alpha DNA was observed in the patients with chromosome 7q32 deletion and translocation, and in one case without detectable chromosome 7 abnormality. HTIF1alpha RNA was found in acute myelocytic leukemic blasts, and was almost undetectable in normal mononuclear cells. The expression varied among the patients: higher in M1 to M3 subtypes, with the highest values in M1; low levels were constantly observed in M4 and M5 AML. In addition, HTIF1alpha was significantly overexpressed in MDS-related AML (MDR-AML), but not in MDS. We also found that HTIF1alpha expression was high in myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells, induced to differentiate along the monocytic-macrophage pathway by TPA or vitamin D3, HTIF1alpha expression decreased, whereas it was maintained at high levels on induction to granulocytic differentiation by RA or DMSO. In K562 cells, HTIF1alpha RNA levels did not change after hemin-induced erythroid differentiation. These results suggest that HTIF1alpha could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages.