Cronbach’s coefficients were good (0 70-0 97) for all scales exce

Cronbach’s coefficients were good (0.70-0.97) for all scales except environment. Correlations between the areas of the QLQ-C30 and OUT-PATSAT35 RT were generally low (<0.40).


between the OS and the IR were moderate with the EORTC OUT-PATSAT35 RT. Areas whose contents were more related had higher correlation coefficients (>0.50), and vice versa (<0.20).

Patients with higher scores on the OS and the IR, patients who had more visits to the doctor and patients who had a better performance status showed higher SC Belnacasan manufacturer levels in 12, 8 and 1 OUT-PATSAT35 RT areas, respectively.

Conclusions: The OUT-PATSAT35 RT appears to be a reliable and valid instrument when applied to a sample of Spanish cancer patients. These results are in line with those of the validation study conducted by the authors of the questionnaire. Copyright (C) 2009 John Wiley & Sons, Ltd.”
“Objective. The criterion commonly used to determine whether radiofrequency neurotomy may be recommended is based on patient-reported, short-term pain relief following

facet block injections. This study evaluated the concordance between two commonly used outcomes for pain relief: the pain numerical rating scale (NRS) and the global perceived improvement (GPI) scale. Design. This is a retrospective cohort study. Methods. Data were obtained from a consecutive cohort of GSK690693 ic50 patients through a review of the electronic medical records, with the following inclusion criteria: medial branch facet blocks at either cervical or lumbar spinal regions. Outcome Measures. Pain NRS (baseline, postprocedure, and hourly up to 6 hours) and GPI scale are expressed as

percent improvement at 6 hours, relative to baseline. Results. The percent improvement in pain NRS corresponded to 49%, 43%, 34%, 21%, and 36% for baseline vs immediately post-block, 1 hour, 3 hours, 6 hours and average of all postscores, respectively. Average GPI reported at 6 hours was 44%, and differed significantly only to the baseline vs 6 hours percent improvement on the NRS (P < 0.01). Multiple regression analysis indicated that there were no demographic or baseline factors that accounted for the discrepancy between GPI vs NRS. Conclusions. Asking patients selleck compound about their pain relief in retrospect can be misleading. It is possible that patients’ report on the GPI is weighed by their total experience of pain reduction and retrospective recall. Therefore, when choosing to address percent improvement on NRS measures, it is important to take into account multiple instances of NRS measures following treatment.”
“Objective: The NCCN Distress Thermometer (DT) was administered to 143 women undergoing chemotherapy for gynecologic cancer over a two-year period. This report describes the frequency and character of psychological distress in this population and examines the effect of disease, treatment, and demographic variables on levels of distress.

A self-consistent analysis was proposed for the prediction of vis

A self-consistent analysis was proposed for the prediction of viscoelastic response of the interphase between PP matrix and CRH particles. A three-phase model was 4-Hydroxytamoxifen chemical structure applied in a reverse mode, and the viscoelastic behavior of the interphase was extracted and compared with the unfilled matrix. Differential scanning calorimetry results indicated that CRH influences crystallization temperature as well as the degree of crystallinity of the composites. An entrapped polymer within CRH filler and PP matrix was detected by scanning electron microscope, which can be

attributed to the interfacial layer with a good adhesion between the main components. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 120: 1642-1651, 2011″
“We present an approach for electrically manipulating nuclear spins in

n-GaAs using an on-chip microcoil. Optically injected spin-polarized electrons are used to generate a dynamic nuclear polarization via electron-nucleus hyperfine interaction with a characteristic check details time constant of similar to 10 min. The saturated Overhauser field amplitude is on the order of several 10 mT and proportional to the spin polarization degree of the injected electrons. Applying an rf field resonant for the As-75 nuclei, complete depolarization of As-75 nuclear spins is observed. (C) 2011 American Institute of Physics. [doi:10.1063/1.3530731]“
“PURPOSE: To evaluate the ultrastructural effect of trypan blue 0.1% staining for capsulorhexis on lens epithelial cells (LECs) and capsules

SETTING: Division of Ophthalmology. University of Sao Paulo, Sao Paulo, Brazil

METHODS: Before capsulorhexis, patients were randomly assigned to 1 of 2

groups Trypan blue 0 1% staining VX-770 molecular weight was performed in the treatment group No trypan blue was used in the control group Samples of capsules with LECs were fixed and analyzed with routine optical microscopy techniques. immunohistochemistry for beclin-1 expression (a marker of autophagy), terminal deoxynucleotidyl transf erase-mediated dUTP-biotin nick-end labeling to detect apoptosis, and transmission electron microscopy (TEM) Morphometric analyses were performed. and the 2 sets of data were compared.

RESULTS: Each group comprised 15 patients Cell death by autophagy and apoptosis was observed in the treatment group but not in the control group The TEM images of subcapsular epithelium cells showed mitochondria’ rupture, dilation of the cisterns of the endoplasmic reticulum, increased cytoplasmic and nuclear electron density, and abnormalities in the nuclear profile of trypan blue-stained cells. Morphometric analysis showed statistically significant differences between the 2 groups in the longest nuclear axes and the ratio between the total nuclear perimeter and the cell area (P = .03) The difference in capsule thickness between groups was not significant.

Study Design: Retrospective case review

Setting: Acad

Study Design: Retrospective case review.

Setting: Academic tertiary care center.

Patients: Seventy-seven severe-to-profoundly deafened adults implanted with one of 5 different internal devices.

Intervention: Cochlear implantation.

Main Outcome Measures: Outcome measures were cochlear implant aided soundfield pure

tone thresholds at 250, 500, 1,000, 2,000, 4,000, and 6,000 Hz.

Results: For the 77 adult patients in the study, pure tone aided AZD1208 cell line thresholds deteriorated over time at 500, 1,000, 2,000, 4,000, and 6,000 Hz at rates ranging from 0.54 to 0.86 dB per year with the implant (p < 0.01). There was no significant change in thresholds over time at 250 Hz (p = 0.30). Overall, 55% of adults showed significantly GSK2126458 mw worse thresholds at 3 or more frequencies. For adults over age 50, the rate of deterioration increased (range, 1.12-1.69 dB per year, p < 0.001), and more of these patients showed significantly worse thresholds at 3 or more frequencies (63%).

Conclusion: This long-term case review shows that a large percentage of implanted adults show a deterioration in aided pure tone thresholds over time. As in presbycusis, this deterioration is most prominent at the highest frequencies; however, the incidence and rate of deterioration is higher than that seen in presbycusis. These physiologic changes are not indicative of device failure and do not mean that performance measures will

necessarily deteriorate.”
“Objective: To assess the efficiency of autologous fat transfer (AFT/Coleman procedure) in the management of velopharyngeal insufficiency (VPI).

Settings: Tertiary academic center, retrospective case series over a 4 year period. Pre- and post-speech assessment by a speech pathologist using the Borel-Maisonny scale.

Patients and method: Twenty-five (25) procedures were performed on 22 patients during the considered period. Mean age at surgery was 12.4 +/- 4.1 years-old. Main associated conditions were 22q11 deletion (n = 6 including 2 with cleft palate), isolated cleft palate (n = 3), and Robin sequence (n = 2).


were VPI grade 2a (n = 5), GW786034 mouse 2b (n = 11) and 3 (n = 6), despite prolonged speech therapy (pre-op mean duration: 4.2 years) and previous surgery (velopharyngoplasty, n = 13). Four patients had a contraindication of velopharyngoplasty (aberrant internal carotid arteries).

Results and conclusion: Fat harvesting sites were umbilicus (n = 23) and buttock (n = 2). Mean injected fat volume was 7.8 ml, in the posterior wall of the pharynx (n = 25) the soft palate (n = 15), the peritonsillar arches (n = 3), and the pre-existing flap (n = 3). Mean follow-up was 17 months. Two patients relapsed once and one patient twice, requiring additional injections. Final post-operative examination 1 year after the last procedure showed an improvement of speech in 90% of cases (grade 1, n = 2; 1/2a, n = 5; 2a n = 10; 2b, n = 5).

01) and LVAD (p = 0 01) patients Adjusted maximum oxygen consump

01) and LVAD (p = 0.01) patients. Adjusted maximum oxygen consumption was higher for HTx patients (p = 0.05) relative to LVAD patients AZD8055 inhibitor at 8 +/- 1 months after implant.

CONCLUSION: HRQoL and exercise capacity increased in both groups over the time-course of the study. After adjusting for relevant variables, HTx patients showed a higher exercise tolerance compared with the LVAD group during follow-up. Thus, future large-scale intervention studies should emphasize the specific needs of these patient

cohorts. J Heart Lung Transplant 2011;30:204-10 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.”
“We investigate the effect of asymmetric grain boundaries (GBs) on the shock response of Cu bicrystals with molecular dynamics simulations. We choose a representative Sigma 3 < 110 > tilt

GB type, (110)(1)/(114)(2), and a grain size of about 15 nm. The shock loading directions lie on the GB plane and are along [00 (1) over bar] and [22 (1) over bar] for the two constituent crystals. The bicrystal is characterized in terms of local structure, shear strain, displacement, stress and temperature during shock compression, and subsequent release and tension. The shock response of the bicrystal manifests pronounced deviation from planar loading as well as strong stress and strain concentrations, due to GBs and the strong anisotropy in elasticity and Stattic plasticity. We explore incipient to full spallation. Voids nucleate either at GBs or on GB-initiated shear planes, and the spall damage also depends on grain orientation. (C) 2010 American Institute of Physics. [doi:10.1063/1.3506707]“
“Obesity is the result of the accumulation of excess body fat and not simply excess weight that can be muscle or fat. Adipocytes function in the adaptation to starvation, in exercise energetics, and in the immune defense against pathogens. Sustained positive energy balance results in excessive accumulation of adipocytes, which, in the abdomen, leads to chronic inflammation. Although informative studies have been performed see more with cultured adipocytes, an

integrative approach to the regulation of abdominal adipose tissue involves feedback from autocrine and paracrine effectors secreted by adipocytes, the immune system, and blood flow through adipose tissue. Numerous adipokines, chemokines, and cytokines feed back to other bodily systems to regulate both energy balance and immune function. Studies of the interactions of the gastrointestinal tract and the central nervous system, as well as psychophysiological considerations of reward circuitry in the central nervous system, have shown a general adaptation to starvation that is opposed to those strategies being proposed for the prevention and treatment of obesity, ie, food restriction and increased physical activity.


This study aimed to investigate the cut-o


This study aimed to investigate the cut-off value of the glucose challenge test in an Iranian population.

Materials and Methods:

A total of 1804 consecutive native Iranian women

who underwent a glucose challenge test were prospectively investigated. The test was performed between 24 and 28 weeks of gestation; each subject received a 50-g oral glucose load regardless of her fasting or fed state; the 1-h venous plasma glucose level was then determined. AZD7762 in vitro Women exceeding 130 mg/dl received the diagnostic 100-g, 3-h oral glucose tolerance test to determine whether or not they had gestational diabetes mellitus.


The prevalence of the glucose challenge test for the whole cohort was 7.2%. The receiver-operator characteristic curve identified a glucose challenge test finding above 135 mg/dl as the cut-off value for detecting gestational diabetes mellitus, which showed a sensitivity and specificity of 95% and 80%, respectively.


Our mTOR inhibitor results suggest that the cut-off value of a 50-g glucose challenge test is 135 mg/dl to identify pregnancies with gestational diabetes mellitus in an Iranian population.”
“Objective: Treatment outcomes for carcinomas of the external auditory canal (EAC) were evaluated regarding radiologic and pathologic factors. Study

Design: Retrospective case review.

Setting: University hospital.

Patients: Fifteen patients histologically diagnosed with

carcinomas of the EAC.

Intervention: A radiologic and pathologic analysis was performed on these patients histologically diagnosed with carcinomas of the EAC and treated surgically at our institution. We evaluated the size of focal defects in the anteroinferior (AI) canal wall of the tympanic bone with preoperative computed tomographic (CT) scans. Histopathologic slides for the same patients learn more were evaluated according to the same criteria as the CT scans.

Main Outcome Measure: Pathologic

features and estimated survival rate.

Results: Preoperative CT scans of 15 temporal bones demonstrated an AI canal wall defect ranging from less than 1 mm to full-thickness destruction. Six of 15 patients had an AI canal wall defect greater than 2 mm on preoperative CT scan. Pathologic findings in these 6 cases showed extension of the tumor through the AI defect into the anterior soft tissues. Information on patients’ survival status was obtained after a median follow-up period of 78.3 months (range, 18-151 mo).

Conclusion: Preoperative CT can be used to accurately determine the pathologic extent of tumor invasion in carcinomas of the EAC. This diagnostic method facilitates exchange of accurate clinical data in a comparable form and can be used to evaluate the efficacy of existing and proposed treatments for EAC tumors.”
“Endovascular treatment for type B dissections is controversial. This therapy aims at complete occlusion and thrombosis of the false lumen of the aneurysm.

1 ng/mL in recently diagnosed and chronic illness males, respecti

1 ng/mL in recently diagnosed and chronic illness males, respectively), and were higher in females with recently diagnosed illness than in females who were chronically ill (P = 0.0002 at endpoint). Prolactin-related events were reported by 7.9% of recently diagnosed subjects with schizophrenia and 3.5% of those who were chronically BEZ235 ic50 ill.

Conclusion: The long-term tolerability of paliperidone palmitate was generally similar in recently diagnosed schizophrenia subjects and those with more chronic illness, with the exception of some prolactin-related measures.”

identify factors associated with an increased likelihood that horses would have a serum Streptococcus equi SeM-specific antibody titer >= 1: 1,600.



Animals-188 healthy client-owned horses.

Procedures-A single serum sample from each horse was tested for SeM-specific antibody titer with an ELISA. Multivariate logistic regression was used to identify factors associated with having a titer >= 1:1,600.

Results-Age, ERK inhibitor in vitro breed, and vaccination status were significantly associated with the likelihood of having a titer >= 1:1,600. The odds of having a titer >= 1:1,600 increased by a factor of 1.07 with each 1-year increase in age. Quarter Horses and horses of other breeds were 4.08 times as likely as were Thoroughbreds and warmbloods to have a titer this high. Horses that had previously received an intranasal S equivaccine were 4.7 times as likely as were horses without any history of vaccination to have a titer this high.

Conclusions and Clinical Relevance-Results indicated that older horses, horses other than Thoroughbreds and warmbloods, and horses that had been vaccinated with an attenuated-live intranasal S equivaccine between 1 and 3 years previously had an increased likelihood of having

a serum SeM-specific antibody titer >= 1:1,600. (J Am Vet Med Assoc 2009;235:973-977)”
“Chronic obstructive pulmonary disease (COPD) is characterized by a persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. From a pathological point of view, COPD is characterized selleck kinase inhibitor by two distinct and frequently coexisting aspects: small airway abnormalities and parenchymal destruction (or emphysema). When pathological changes are localized in lung parenchyma, they will contribute to airflow limitation by reducing the elastic recoil of the lung through parenchymal destruction, as well as by reducing the elastic load applied to the airways through destruction of alveolar attachments. Conversely, when pathological changes involve the small airways, they will contribute to airflow limitation by narrowing and obliterating the lumen and by actively constricting the airways, therefore increasing the resistance.

Presence of intraventricular hemorrhage was not associated with p

Presence of intraventricular hemorrhage was not associated with poor outcome, but hydrocephalus showed a trend (P = .09) toward poor outcome. In receiver operating characteristic curve analysis, combined intraparenchymal hemorrhage and intraventricular hemorrhage volume also showed a trend toward better outcome prediction than intraparenchymal hemorrhage volume alone. Although not an independent outcome predictor, future studies should assess intraventricular hemorrhage qualitatively

and quantitatively.”
“Study Design. Prospective radiological and clinical study with scoliosis patients.

Objective. To determine the pre- and postoperative differences in the three-dimensional (3D) parameters and relationships with the outcome in scoliosis surgery.

Summary of SB202190 in vitro Background Data. Despite a proven important role of the 3D deformities in scoliosis, it is warranted to confirm the efficacy of these measurements, which carry a cost burden and radiation hazard.


Fifty adolescent idiopathic scoliosis patients who underwent correction surgery were enrolled in this study. Pre- and postoperative whole spine radiographs and computed tomography were performed. The vertebral rotation AZD1480 (VR), rib hump index (RH), sternal shift (SS) on computed tomography were measured at the level of the apex in each patient. In addition, the patients described the SRS 30 (scoliosis research society 30) and ODI (owestry disability index) score. And, the differences in the parameter and the relationships between the radiological and clinical outcomes were analyzed.

Results. There was significant decrease in the coronal curvature, RH, and SS after surgery (P < 0.0001). In addition, the VR decreased postoperatively but that was not significant (P = 0.236). There were significant relationships between the parameters in the coronal curvature, VR, RH, and SS, pre- and postoperatively (P < 0.05). However, regarding the pre- and postoperative differences, only the changes in the SS were related to changes in BKM120 clinical trial the coronal curvature (P = 0.006). In addition, there were significant relationships between the parameters and outcomes. The changes

in ODI were related to changes in the coronal curvature, VR, RH, and SS (P < 0.0001, P = 0.039, P < 0.0001, P = 0.019, respectively). However, the changes in the SRS was only related to the changes in SS (P < 0.0001).

Conclusion. There were significant correlations between the VR, RH, and SS with the coronal curvature, pre- and postoperatively. In addition, there were significant correlations between the 3D deformities and outcomes. Computed tomography based measurements of 3D deformities can provide useful information in planning, and predicting the outcome of corrective surgery.”
“This article reviews the treatment goals and efficacy of comprehensive pain rehabilitation programs for the treatment of chronic headache.

Therefore, CCHL should be studied further as a promising candidat

Therefore, CCHL should be studied further as a promising candidate Selleckchem Selumetinib of burn treatment dressing against MRSA infections for clinics.”
“Speciation in animals often requires that population divergence goes through three major evolutionary stages, i.e. ecological divergence, development of sexual isolation and the build-up of genetic incompatibility. There is theoretical consensus regarding favourable

conditions required for speciation to reach its final and irreversible stage, but empirical tests remain rare. Here, we review recent research on processes of speciation, based on studies in hybrid zones between collared (Ficedula albicollis) and pied flycatchers (Ficedula hypoleuca). BTK pathway inhibitors A major advantage of this study system is that questions concerning

all three major sources of reproductive isolation and their interconnections can be addressed. We conclude that (i) ecological divergence is caused by divergence in life-history traits, (ii) females prefer mates of their own species based on differences in both plumage and song characteristics, (iii) male plumage characteristics have diverged but their song has converged in sympatry, (iv) there is genetic incompatibility in accordance with Haldane’s rule, and (v) the Z-chromosome appears to be a hotspot for genes involved in sexual isolation and genetic incompatibility. We discuss how identification of the genes underlying the three major sources of reproductive isolation can be used to draw conclusions about links between the

processes Compound C clinical trial driving their evolution.”
“The isothermal and nonisothermal crystallization and the subsequent melting behaviors of the polypropylene (PP) component in the in-reactor alloy were studied systematically by a series of thermal analysis techniques. The alloy sample used in the present study is a newly invented in situ blend of polypropylene with high ethylene-propylene rubber content. The effect of annealing temperatures on the subsequent crystallization and melting process of PP was explained by the different molecular behavior in the three “”temperature domains.”" Multiple melting endotherms were also observed for the nonisothermally crystallized sample, and were attributed to the dynamic melting process which consists of three steps: melting, recrystallization, and remelting. The melting temperature of initial mesomorphic phase is found to be very close to the temperature of recrystallization or reorganization. To separate the recrystallization process from the overlapping processes, the difference spectra of fast and slow heated DSC endotherms were used, which is based on a straight forward but reasonable assumption. In addition, temperature modulated differential scanning calorimetry (TMDSC) has also been used to study the melting of PP component. (C) 2011 Wiley Periodicals, Inc.

In case 1, the patient was a 33-year-old woman who had developed

In case 1, the patient was a 33-year-old woman who had developed pale red papules on her face, especially around her eyes and lower jaw, approximately PFTα Apoptosis inhibitor 7 months previously. Examination of

a skin biopsy specimen revealed epithelioid cell granulomas accompanied by caseous necrosis, and a diagnosis of LMDF was made. The patient was treated successively with azithromycin, roxithromycin and minocycline hydrochloride, but there was no improvement. When we tried oral tranilast therapy, flattening of the papules was observed 2 weeks after the start of treatment, and by 1 month the papules had almost disappeared. In case 2, the patient was a 39-year-old man who had broken out in erythematous papules on both upper and lower eyelids, with some accompanied by scaling, 2 years before the initial examination. Pathological specimen revealed epithelioid cell granulomas accompanied by caseous necrosis, and a diagnosis of LMDF was made. There was no improvement when treated orally with minocycline hydrochloride or doxycycline hydrochloride, and treatment was switched to oral tranilast therapy. After 1 month of treatment, the papules had almost disappeared. We concluded that oral tranilast therapy should be tried as a treatment for intractable LMDF.”
“Purpose: To evaluate glomerular injury in the rat model

during renal warm ischemia (WI), comparing artery and vein (AV) clamping with artery only (AO) clamping.

Materials and Methods: Twenty-four adult male rats underwent 60 minutes of renal WI in the left kidney. The animals were divided into three groups: AV clamping, Tipifarnib ic50 AO clamping, and Sham surgery. After 30 days, the animals were euthanized, and both kidneys were processed for paraffin embedding and stained with hematoxylin and eosin. Glomerular volume density (Vv[glom]), mean glomerular volume (MGV), and number of glomeruli per mm(3) (Nv[glom]) were evaluated in the renal cortex.

Results: The Vv[glom] was reduced in the left kidney (ischemic) when

compared with the right kidney in both AV and AO groups by 11.1% and 35.4%, respectively; however, the difference was significant only in the AV group. The Nv[glom] was reduced in the left kidney when compared with the right kidney in both AV and AO groups by 11.6% and 31.4%, respectively; nevertheless, the difference was significant only in the AV group. The MGV of left and right kidneys was the same in both Sham and AO groups and was diminished by 6.7% in the AV group-not significant.

Conclusion: AV clamping causes a significant decrease in the number of glomeruli in the rat model, while AO clamping reduces the glomerular number, but not significantly. To minimize renal injury, AO clamping may be preferred over AV clamping when WI is necessary in patients with previously compromised renal function.

The life-history characteristics of Botryllus make it an excellen

The life-history characteristics of Botryllus make it an excellent model to dissect the functional and developmental mechanisms underlying allorecognition, and have the potential to reveal novel insights into issues from innate recognition strategies to the evolution of genetic polymorphism. In addition, we hypothesize that allorecognition

in Botryllus must be based on conserved processes that are fundamental to all immune function: education and tolerance, or the ontogeny and maintenance of specificity.”
“The polarization switching transients of spray deposited ferroelectric (NH4)(0.391)K0.61NO3 (NKN) films has been analyzed with nucleation limited switching (NLS) model by considering domain growth limited GW786034 process. The experimentally measured microscopic polarization switching curves fitted well with NLS model and the characteristic switching times obeyed the Lorentzian distribution function. The local field variation was found to be minimum at pulse amplitude 15 V, which makes the polarization reversal more probable. The value of spontaneous polarization, P-s and coercive field, E-c was found to be 6.58 mu C/cm(2) and 4.10 kV/cm, respectively.

The value of Ps from the switching and P-E loop is in good agreement with each other. The field emission scanning electron microscopy and atomic force microscopy images of the NKN film reveal the formation of nanoparticles of NKN. (C) 2010 American Institute NSC 66389 of Physics. SNX-5422 [doi:10.1063/1.3457228]“
“Mei-gui Hua has been used as a crude drug in traditional medicine and as herbal tea in China. The scientific name of Mei-gui is Rosa rugosa thunb. However, the morphological characteristics and botanical ecology of Mei-gui were different from

those of R. rugosa. Since the botanical origins of Mei-gui cultivated in China have not yet been clarified, we compared Mei-gui and R. rugosa in terms of their morphological characteristics, phylogenetic analysis, and phytochemical studies. Our research suggested that Mei-gui cultivated around Tarim Basin in Xinjiang Province showed homology to Rosa gallica, while those cultivated in the northeastern parts of China are considered to be hybrids of R. rugosa.”
“Sporadic diseases, which occur as single, scattered cases, are among the commonest causes of human morbidity and death. They result in a variety of diseases, including many cancers, premature aging, neurodegeneration and skeletal defects. They are often pathogenetically complex, involving a mosaic distribution of affected cells and are difficult to model in the mouse. Faithful models of sporadic diseases require innovative forms of genetic manipulation to accurately recreate their initiation and pathogenesis. Such modelling is crucial to understanding these diseases and, by extension, to the development of therapeutic approaches to treat them.