ABSTRACT
The anteromedial temporal region and the lateral wall of the sphenoid can be the site of an array of pathology including trigeminal schwannoma, encephalocele, cholesterol granuloma of the petrous apex, malignancy, infection, and sellar pathology extending to the lateral cavernous sinus. Approaches to this region are technically challenging and the existing approach requires sacrifice of all of the turbinates including the nasolacrimal duct, which can cause postoperative complications. We describe a novel anatomical landmark between the periorbita and the periosteum of the pterygopalatine fossa (which is located at the inferolateral periorbital periosteal line [ILPPL]). The posterior one-third of the incision line lies between the foramen rotundum and the superior orbital fissure, which is proximal to the maxillary strut. A 1.5-cm incision can divide the orbital and pterygoid contents and lead us to the posterior inferolateral orbital region, anteromedial temporal region, lateral wall of the sphenoid sinus, and lateral wall of the cavernous sinus. A combined multiangled approach to the ILPPL will enable us to preserve all of the turbinates and the septum, and the nasolacrimal duct, allowing for the preservation of the physiological function and pedicled flaps, such as the middle turbinate, inferior turbinate, and septal membrane flap. The ILPPL is a simple, effective, and novel landmark for the minimally invasive approach to the anteromedial temporal fossa.
ABSTRACT
A critical procedure in the transcribriform approach is the resection of the crista galli. However, the standard technique for crista galli resection has several disadvantages. We reviewed the cases of patients with olfactory neuroblastomas who underwent an endoscopic endonasal transcribriform approach using a newly developed technique for crista galli resection. We performed a cadaveric study to measure the superior accessibility limits using the proposed method. We included 38 patients with olfactory neuroblastomas in this study. The tumor invaded the posterior crista galli in four patients. The anterior end of the crista galli was not invaded by the tumor. Our cadaveric study showed that the dura was approachable to the point that was 7.4 ± 1.3 mm superior and 23.2 ± 7.2 mm lateral to the foramen cecum following crista galli removal. By resecting the crista galli in advance, manipulation of the superior dura became feasible.
Subject(s)
Esthesioneuroblastoma, Olfactory , Nose Neoplasms , Humans , Cadaver , Ethmoid Bone , Nasal Cavity/surgeryABSTRACT
The interaction between the tumor suppressor protein p53 and its negative regulator, the MDM2 oncogenic protein, has gained significant attention in cancer drug discovery. In this study, 120 lignans reported from Ferula sinkiangensis and Justicia procumbens were assessed for docking simulations on the active pocket of the MDM2 crystal structure bound to Nutlin-3a. The docking analysis identified nine compounds with higher docking scores than the co-crystallized reference. Subsequent AMDET profiling revealed satisfactory pharmacokinetic and safety parameters for these natural products. Three compounds, namely, justin A, 6-hydroxy justicidin A, and 6'-hydroxy justicidin B, were selected for further investigation due to their strong binding affinities of -7.526 kcal/mol, -7.438 kcal/mol, and -7.240 kcal/mol, respectively, which surpassed the binding affinity of the reference inhibitor Nutlin-3a (-6.830 kcal/mol). To assess the stability and reliability of the binding of the candidate hits, a molecular dynamics simulation was performed over a duration of 100 ns. Remarkably, the thorough analysis demonstrated that all the hits exhibited stable molecular dynamics profiles. Based on their effective binding to MDM2, favorable pharmacokinetic properties, and molecular dynamics behavior, these compounds represent a promising starting point for further refinement. Nevertheless, it is essential to synthesize the suggested compounds and evaluate their activity through in vitro and in vivo experiments.
Subject(s)
Antineoplastic Agents , Lignans , Plants, Medicinal , Molecular Docking Simulation , Molecular Dynamics Simulation , Reproducibility of Results , Tumor Suppressor Protein p53 , Antineoplastic Agents/pharmacology , Lignans/pharmacologyABSTRACT
INTRODUCTION: Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War Illness (GWI). Since the apolipoprotein E (APOE) ε4 allele is associated with the risk of cognitive decline with age, particularly in the presence of environmental exposures, and cognitive impairment is one of the most common symptoms experienced by veterans with GWI, we examined whether the ε4 allele was associated with GWI. METHODS: Using a case-control design, we obtained data on APOE genotypes, demographics, and self-reported GW exposures and symptoms that were deposited in the Boston Biorepository and Integrative Network (BBRAIN) for veterans diagnosed with GWI (n = 220) and healthy GW control veterans (n = 131). Diagnosis of GWI was performed using the Kansas and/or Center for Disease Control (CDC) criteria. RESULTS: Age- and sex-adjusted analyses showed a significantly higher odds ratio for meeting the GWI case criteria in the presence of the ε4 allele (Odds ratio [OR] = 1.84, 95% confidence interval [CI = 1.07-3.15], p ≤ 0.05) and with two copies of the ε4 allele (OR = 1.99, 95% CI [1.23-3.21], p ≤ 0.01). Combined exposure to pesticides and PB pills (OR = 4.10 [2.12-7.91], p ≤ 0.05) as well as chemical alarms and PB pills (OR = 3.30 [1.56-6.97] p ≤ 0.05) during the war were also associated with a higher odds ratio for meeting GWI case criteria. There was also an interaction between the ε4 allele and exposure to oil well fires (OR = 2.46, 95% CI [1.07-5.62], p ≤ 0.05) among those who met the GWI case criteria. CONCLUSION: These findings suggest that the presence of the ε4 allele was associated with meeting the GWI case criteria. Gulf War veterans who reported exposure to oil well fires and have an ε4 allele were more likely to meet GWI case criteria. Long-term surveillance of veterans with GWI, particularly those with oil well fire exposure, is required to better assess the future risk of cognitive decline among this vulnerable population.
Subject(s)
Apolipoproteins E , Persian Gulf Syndrome , Persian Gulf Syndrome/genetics , Humans , Apolipoproteins E/genetics , Veterans , Pyridostigmine Bromide/toxicity , Pesticides/toxicity , Hazardous Substances/toxicity , Male , Female , Middle Aged , Smoke/adverse effectsABSTRACT
Low birth weight (LBW) is an important indicator of maternal health and poverty. This study explored the socioeconomic factors associated with LBW. METHODS: Data was collected from a 4-year maternal-newborn registry. RESULTS: There were 5,316 LBW and 54,029 normal birth weight (NBW). The prevalence of LBW was 9%. The Native women in the LBW group compared to non-native women were 10.4% (1784/5316) vs. 8.4% (3532/5316) with a P-value of 0.001. There were more illiterate mothers in the LBW compared to the NBW, respectively: 8.1% (1597/19497) vs. 7.5% (1763/23230) with a P-value of 0.001. Working mothers tend to have more LBW infants compared to mothers with NBW, 8.4% (1588/17217) vs. 7.9% (2532/31891) and P-value 0.001. Young mothers (<20 years old) with early childbearing had more LBW compared to older mothers, respectively 12.7% (180/1414) vs. 8.9% (5149/52919) P-value <0.001. Women with no antenatal care reported a high rate of LBW compared to women with regular antenatal care: 14.2% (516/3696) vs. 8.6% (4741/55691) P-value <0.001. LBW babies were born more from assisted conception pregnancies (38% compared to 8.4% of normal pregnancies) P-value <0.001. Smoking mothers scored higher with LBW at 13.6% vs. 8.3% and a P-value of 0.001. There were no differences between the two groups regarding religion, consanguinity, marital status, or family income. CONCLUSION: Risk factors for low birth weight can be improved by providing antenatal care, smoking cessation, optimizing high-risk pregnancy care, and governing assisted reproduction regulations.
Subject(s)
Infant, Low Birth Weight , Mothers , Pregnancy , Infant, Newborn , Female , Humans , Young Adult , Adult , Birth Weight , Socioeconomic Factors , Risk FactorsABSTRACT
Granulomatosis with polyangiitis is a rare autoimmune disease that affects small to medium-sized blood vessels throughout the body. Here, we present a case of an infratemporal mass that was the result of granulomatosis with polyangiitis. A 51-year-old male presented to the emergency department due to right cheek and facial pain that he had been experiencing for 2 to 3 months. An MRI revealed a mass within the right infratemporal and pterygopalatine fossae extending into the inferior right orbital fissure along the maxillary division of the trigeminal nerve (V2) and the vidian nerve causing concern for malignancy. Histology from an endoscopic biopsy demonstrated multiple arteries with luminal obliteration with non-necrotizing granulomas. The patient was started on steroids and immunosuppressive therapy, which improved his symptoms and decreased the size of the residual mass. This case illustrates the need for laboratory testing, imaging, and biopsy of the involved tissue in cases where GPA is suspected to prevent treatment delays that could lead to the destruction of vital organs.
ABSTRACT
Background and objectives: The World Health Organization (WHO) announced the appearance of a new coronavirus disease in Hubei province, China, to be a public health emergency of international concern. The objectives of this study can be highlighted through classifying the information sources for identifying protective practices, death probability, gender-death associations probability and education level. Methodology: This is a descriptive design study conducted among the Kurdistan Region/Iraq population via an online application between 1 March and 1 May 2020. Three hundred twenty people participated in this questionnaire study. The data were collected through an online form, relying upon a self-report questionnaire. The questionnaire had three main parts. The first part is related to the socio-demographic characteristics of the sample, including gender, age, family status, address status and education level. The second part involves the items related to precautionary measures using none, sometimes, and always. The last part contains items related to death probability owing to other causes and this includes five categories: extremely low, low, intermediate, high and extremely high. The validity and reliability of this questionnaire were revised by the panel of experts before the data collection. Results: The outcomes of the study revealed that the majority, ca. 73%, of the Kurdistan Region/Iraq population depended on TV to obtain information about COVID-19. Also, this investigation showed that there is a substantial association between participants with infection prevention and control practices relevant to COVID-19. Moreover, according to this study, there is a significant relationship between the death probability and COVID-19. Concurrently, there is not any significant association between other causes, namely cancer, heart diseases, diabetes and road traffic accidents, and the death probability. Conclusion: This study showed that for the majority of the Kurdistan Region/Iraq population the most reliable source of information for any COVID-19 related updates is the TV broadcast. This study also indicated that there is strong association for the majority of individuals regarding their practices for prevention from COVID-19 and death probability with COVID-19. However, there is not any substantial association between the epidemic and the other deadly calamities and the death probability.
ABSTRACT
In southwest Florida, Karenia brevis (K. brevis) blooms occur frequently, can be very intense and persist over several years. Individuals living in coastal communities around the Gulf of Mexico are particularly vulnerable to brevetoxins released by K. brevis in seawater and carried inland within marine aerosol. Exposure to K. brevis occurs during residential, recreational, and occupational activities and has been associated with upper respiratory tract (URT) symptoms in healthy and medically vulnerable individuals. Additionally, ingestion of brevetoxin-contaminated seafood causes neurotoxic shellfish poisoning (NSP), and severe headaches prompting emergency department visits which occur in excess during K. brevis blooms. The current study examined a dose-response relationship between K. brevis in coastal waters and URT and NSP-like symptoms and headaches among southwest Florida residents. Data on past medical history (PMH) and medical symptoms were collected from the participants (n = 258) in five southwest Florida counties between June 2019 to August 2021. A dose-response relationship was observed between K. brevis blooms and reporting of URT and NSP-like symptoms and headaches. Reporting of NSP-like symptoms was higher among participants with a PMH of migraines, chronic fatigue syndrome (CFS) and mild memory loss, while the association of headaches with K. brevis blooms was accentuated among individuals with a PMH of migraines. These results suggest further investigations into the threshold of aerosolized brevetoxin dose required to elicit URT, headaches and/or NSP-like symptoms. These symptoms ultimately cause significant public health safety concerns, primarily among vulnerable populations with preexisting neurological conditions.
Subject(s)
Dinoflagellida , Migraine Disorders , Shellfish Poisoning , Headache , Humans , Neurotoxins , Respiratory SystemABSTRACT
Jatropha oil-based polyurethane acylate gel polymer electrolyte was mixed with different concentrations of tetrabutylammonium iodide salt (TBAI). The temperature dependences of ionic conductivity, dielectric modulus and relaxation time were studied in the range of 298 to 393 K. The highest ionic conductivity of (1.88 ± 0.020) × 10-4 Scm-1 at 298 K was achieved when the gel contained 30 wt% of TBAI and 2.06 wt% of I2. Furthermore, the study found that conductivity-temperature dependence followed the Vogel-Tammann Fulcher equation. From that, it could be clearly observed that 30 wt% TBAI indicated the lowest activation energy of 6.947 kJ mol-1. By using the fitting method on the Nyquist plot, the number density, mobility and diffusion coefficient of the charge carrier were determined. The charge properties were analysed using the dielectric permittivity, modulus and dissipation factor. Apart from this, the stoke drag and capacitance were determined.
Subject(s)
COVID-19 , Interferon Type I , Psoriasis , COVID-19 Vaccines , Humans , Psoriasis/chemically induced , SARS-CoV-2ABSTRACT
AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.
Subject(s)
Persian Gulf Syndrome/pathology , Boston , Humans , Information Dissemination , Magnetic Resonance Imaging , Persian Gulf Syndrome/blood , Positron-Emission Tomography , Saliva/metabolismABSTRACT
In this paper, the adsorptive performance of synthesized thiourea (TU) modified poly(acrylonitrile-co-acrylic acid) (TU-P(AN-co-AA)) polymeric adsorbent for capturing p-nitrophenol (PNP) from aqueous solution was investigated. TU-P(AN-co-AA) was synthesized via the redox polymerization method with acrylonitrile (AN) and acrylic acid (AA) as the monomers, then modified chemically with thiourea (TU). Characterization analysis with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), elemental microanalysis for CHNS, zeta potential measurement, Brunauer-Emmett-Teller (BET) surface analysis and thermal analyses were carried out to determine the morphology and physico-chemical properties of the synthesized polymer. The characterization results indicated successful surface modification of polymer with TU. The performance of TU-P(AN-co-AA) for the removal of PNP was investigated under various experimental parameters (adsorbent dosage, initial adsorbate concentration, contact time and temperature). The results demonstrated that the Freundlich isotherm model and pseudo-second-order kinetic model best described the equilibrium and kinetic data, respectively. Thermodynamic studies showed that the uptake of PNP by TU-P(AN-co-AA) was spontaneous and exothermic in nature. The results of the regeneration studies suggested that the TU-P(AN-co-AA) polymer is a reusable adsorbent with great potential for removing PNP from wastewater.
Subject(s)
Acrylonitrile , Water Pollutants, Chemical , Acrylates , Adsorption , Hydrogen-Ion Concentration , Kinetics , Nitrophenols , Spectroscopy, Fourier Transform Infrared , Thermodynamics , Thioamides , Water Pollutants, Chemical/analysisABSTRACT
Background: Healthcare Workers (HCWs) constitute a major group exposed to influenza. Researchers herein try to determine the influenza vaccine effectiveness (VE). Influenza VE depends on the vaccinated personal characteristics and the closeness of matching between the vaccine and the prevalent strains of the virus. The aim of our research was to identify the 2018-2019 seasonal influenza VE in HCWs. Methods: a record-based study was carried out using the test-negative design from October 2018 to September 2019 to calculate the influenza VE. HCWs with influenza like illness (ILI) were screened to detect the positive cases, and the vaccination status was determined based on vaccination database. VE was assessed from the ratio of the odds of vaccination among positive cases to the odds of vaccination among negative controls. Statistical analysis Multivariable logistic regression was used to estimate adjusted VE Results: a total of 556 HCWs presented with ILI, 65.6% were females, and 54.1% were nurses, 152 HCWs (27.3%) had laboratory-confirmed influenza, shows two peaks in January and March 2019. VE for all types was 35.0% and rose to 42.0% after adjustment for HCWs age, gender, nationality, and job position, influenza A (H3N2) VE was 78.0%. H1N1 VE was 55.0% but no significant VE for type B was found. Conclusion: Our VE estimates are in agreement with VE estimates published for that season. The use of quadrivalent vaccine with two stains of influenza B is recommended.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Military Personnel , Case-Control Studies , Female , Health Personnel , Humans , Influenza A Virus, H3N2 Subtype , Influenza B virus , Influenza, Human/prevention & control , Male , Seasons , VaccinationABSTRACT
BACKGROUND AND OBJECTIVE: Indigofera zollingeriana leguminous have been known widely to have a concentrate feed characteristic due to its high nutrient contents (crude protein, vitamin and some mineral) and its highly dry matter (DM) digestibility. This study aimed to identify the effects body weight gain, nutrients degradability, fermentation rumen characteristics and blood metabolite of Boerka goat supplemented green concentrate pellets (GCP)based on Indigofera zollingeriana. MATERIALS AND METHODS: Twenty four male Boer x Kacang crossbreeds with age of approximately male phase to 6 months and average initial body weight (BW) 13±0.5 kg were used in feeding and degestion trials. The study was assigned according to randomized block design with four dietary treatments and six goats were allocated to one of four treatments in randomised block design. The animals feed was offered chopped fresh Brachiaria humidicola (ad libitum) and feed treatments were offered daily at 4.0% body weight (BW). RESULTS: The digestibility increased in line with the increasing proportion of I. zollingeriana in the green concentrate pellets (GCP). The tannin content of GCP seemed to not significantly impacted on feed intake. The daily body weight gain and efficiency of feed utilization increased as the proportion of I. zollingeriana GCP increased. Increasing of the proportion C. calotyhrsus in GCP affected the concentration of ammonia (NH3) and VFA of the rumen liquids of goat. CONCLUSION: Green concentrate pellets composing 90% I. zollingeriana gave the best results in term of daily body weight gain, feed intake, nutrient degradability, efficiency of feed utilization, rumen fermentation in Boerka goats.
Subject(s)
Body Weight/drug effects , Fermentation/drug effects , Indigofera/metabolism , Nutrients/metabolism , Rumen/drug effects , Weight Gain/drug effects , Ammonia/metabolism , Animal Feed , Animal Nutritional Physiological Phenomena/drug effects , Animals , Diet , Dietary Supplements , Digestion/drug effects , Goats , Male , Rumen/metabolism , Tannins/metabolismABSTRACT
Tat-interacting protein of 60 kDa (TIP60) is an essential lysine acetyltransferase implicated in transcription, DNA damage response and apoptosis. TIP60 protein expression is reduced in cancers. In cervical cancers, human papillomavirus (HPV) E6 oncogene targets cellular p53, Bak and some of the PDZ domain-containing proteins for proteasome-mediated degradation through E6AP ligase. Recently, E6 oncogene from high-risk and low-risk categories was also shown to target TIP60. However, the molecular mechanisms and whether destabilization of TIP60 contributes to HPV E6-mediated transformation remain unanswered. Our proteomic analyses revealed EDD1 (E3 identified by differential display), an E3 ligase generally overexpressed in cancers as a novel interacting partner of TIP60. By investigating protein turnover and ubiquitination assays, we show that EDD1 negatively regulates TIP60's stability through the proteasome pathway. Strikingly, HPV E6 uses this function of EDD1 to destabilize TIP60. Colony-formation assays and soft agar assays show that gain of function of TIP60 or depletion of EDD1 in HPV-positive cervical cancer cells significantly inhibits cell growth in vitro. This phenotype is strongly supported by the in-vivo studies where re-activation of TIP60 in cervical cancer cells dramatically reduces tumor formation. In summary, we have discovered a novel ligase through which E6 destabilizes TIP60. Currently, in the absence of an effective therapeutic vaccine for malignant cervical cancers, cervical cancer still remains to be a major disease burden. Hence, our studies implying a distinct tumor suppressor role for TIP60 in cervical cancers show that reactivation of TIP60 could be of therapeutic value.
Subject(s)
Histone Acetyltransferases/metabolism , Oncogene Proteins, Viral/genetics , Oncogenes , Papillomaviridae/genetics , Ubiquitin-Protein Ligases/metabolism , Cell Division/genetics , Cell Line , Genes, Tumor Suppressor , Humans , Lysine Acetyltransferase 5 , Protein Binding , Proteomics , Ubiquitin-Protein Ligases/geneticsABSTRACT
As Malaysia is one of the world's largest producer of palm oil, large amounts of palm oil mill effluent (POME) is generated. It was found that negatively charged components are accountable for POME color. An attempt was made to remove residual contaminants after conventional treatment using anion base resin. Adsorption experiments were carried out in fixed bed column. Various models such as the Thomas, the Yoon-Nelson, the Wolborska and BDST model were used to fit the experimental data. It was found that only the BDST model was fitted well at the initial breakthrough time. A wavelet neural network model (WNN) was developed to model the breakthrough curves in fixed bed column for multicomponent system. The results showed that the WNN model described breakthrough curves better than the commonly used models. The effects of pH, flow rate and bed depth on column performance were investigated. It was found that the highest uptake capacity was obtained at pH 3. The exhaustion time appeared to increase with increase in bed length and decrease in flow rate.
Subject(s)
Color , Industrial Waste , Neural Networks, Computer , Plant Oils/chemistry , Wastewater/chemistry , Adsorption , Palm Oil , Spectroscopy, Fourier Transform InfraredABSTRACT
BACKGROUND: Nilvadipine may lower rates of conversion from mild-cognitive impairment to Alzheimer's disease (AD), in hypertensive patients. However, it remains to be determined whether treatment with nilvadipine is safe in AD patients, given the higher incidence of orthostatic hypotension (OH) in this population, who may be more likely to suffer from symptoms associated with the further exaggeration of a drop in BP. OBJECTIVE: The aim of this study was to investigate the safety and tolerability of nilvadipine in AD patients. METHODS: AD patients in the intervention group (n = 56) received nilvadipine 8 mg daily over 6-weeks, compared to the control group (n = 30) who received no intervention. Differences in systolic (SBP) and diastolic (DBP) blood pressure, before and after intervention, was assessed using automated sphygmomanometer readings and ambulatory BP monitors (ABP), and change in OH using a finometer. Reporting of adverse events was monitored throughout the study. RESULTS: There was a significant reduction in the SBP of treated patients compared to non-treated patients but no significant change in DBP. Individuals with higher initial blood pressure (BP) had greater reduction in BP but individuals with normal BP did not experience much change in their BP. While OH was present in 84% of the patients, there was no further drop in BP recorded on active stand studies. There were no significant differences in adverse event reporting between groups. CONCLUSION: Nilvadipine was well tolerated by patients with AD. This study supports further investigation of its efficacy as a potential treatment for AD.
Subject(s)
Alzheimer Disease/drug therapy , Antihypertensive Agents/adverse effects , Blood Pressure/drug effects , Nifedipine/analogs & derivatives , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Nifedipine/adverse effectsABSTRACT
Several independent studies have reported that loci on chromosome 10 are associated/linked with Alzheimer's disease (AD), including a family-based study demonstrating an association between the marker D10S583 and AD. We have examined the D10S583 polymorphic marker and apolipoprotein E (APOE) gene in a case-control study. We observed the expected association of the APOE allele varepsilon4 with AD, and an inverse association between the D10S583 allele 209 and AD. These data support the original findings that suggest the presence of a candidate gene for AD in this region of chromosome 10. The nearby insulin degrading enzyme gene has been previously proposed as a candidate gene; however, a number of other putative candidate genes are also located in this region. The ongoing investigation of the genetic source of association and linkage in this region is clearly warranted.