Previous studies showed that introduction of mesenchymal stem cells (MSCs) modified by FVIII-expressing retrovirus may result in phenotypic correction of HA animals. This study aimed at the investigation of an alternative gene therapy strategy that may lead to sustained FVIII transgene expression in HA mice. B-domain-deleted human FVIII (hFVIIIBD) vector was microinjected into single-cell embryos of wild-type mice to generate a transgenic mouse line, from which hFVIIIBD-MSCs were isolated, followed by transplantation

into HA mice. RT-PCR and real-time PCR analysis demonstrated the expression of hFVIIIBD in multi-organs of recipient HA mice. Immunohistochemistry showed the presence of hFVIIIBD positive staining in multi-organs of recipient HA mice. ELISA indicated that plasma hFVIIIBD level in selleckchem recipient mice reached its peak (77 ng/mL) at the 3rd week after implantation, and achieved sustained expression

during the 5-week observation period. Plasma FVIII activities of recipient HA mice increased from 0% to 32% after hFVIIIBD-MSCs transplantation. APTT (activated partial thromboplastin time) value decreased in hFVIIIBD-MSCs transplanted EGFR inhibitor review HA mice compared with untreated HA mice (45.5 s vs. 91.3 s). Our study demonstrated an effective phenotypic correction in HA mice using genetically modified MSCs from hFVIIIBD transgenic mice.”
“Raloxifene HCl (RH), a selective estrogen receptor modulator (SERM), is indicated for the prophylaxis or treatment of postmenopausal osteoporosis. RH shows extremely poor bioavailability due to limited solubility and an extensive intestinal/hepatic first-pass metabolism. Solid lipid nanoparticles (SLNs) are valuable carriers

that can enhance drug bioavailability. However, in the case of RH, the encapsulation of the drug in SLNs remains a challenge because of its poor solubility in both water and lipids. In this study, a series of RH-containing SLNs (RH-SLNs) were generated using a modified double emulsion solvent evaporation (DESE) method. Briefly, RH with various drug/lipid ratios was solubilized in the inner core of a double BIX 01294 solubility dmso emulsion using different water/organic solvent mixtures. Our best formulation was achieved with the formation of negatively charged nanoparticles, 180 nm in diameter, with an encapsulation and loading efficiency of 85% and 4.5%, respectively. It also showed a Fickian mechanism of the drug release in the basic dissolution media. Thermal analysis revealed a distinct decrease in the crystallinity of lipids and RH in comparison with the unprocessed materials. The results of a cell viability assay also showed a better antiproliferative effect of the drug-loaded SLNs versus the free drug solution. Thus, these results indicated that the modified DESE method could be proposed for the effective encapsulation of RH in SLNs with appropriate physicochemical and biological properties.

Methods. We conducted a multisite

cohort study of 3672 antiretroviral-naive patients initiating antiretroviral therapy (ART) during 2000-2010. Retention in care was measured by the IOM and DHHS core indicators (2 attended visits at defined intervals per 12-month period), and also as a count of missed primary Selleckchem PF-6463922 HIV care visits (no show) during a 24-month measurement period following ART initiation. All-cause mortality was ascertained by query of the Social Security Death Index and/or National Death Index, with adjusted survival analyses starting at 24 months after ART initiation. Results. Among participants, 64% and 59% met the IOM and DHHS retention core indicators, respectively, Selleckchem BTK inhibitor at 24 months.

Subsequently, 332 patients died during 16 102 person-years of follow-up. Failure to achieve the IOM and DHHS indicators through 24 months following ART initiation increased mortality (hazard ratio [HR] = 2.23; 95% confidence interval [CI], 1.79-2.80 and HR = 2.36; 95% CI, 1.89-2.96, respectively). Among patients classified as retained by the IOM or DHHS clinical core indicators, bigger than 2 missed visits further increased mortality risk (HR = 3.61; 95% CI, 2.35-5.55 and HR = 3.62; 95% CI, 2.30-5.68, respectively). Conclusions. Beyond HIV retention core indicators, missed clinic visits were independently associated with all-cause mortality. Caution is warranted in relying solely

upon retention in care core indicators for policy, clinical, and programmatic purposes.”
“Oxidation of DNA due to exposure to reactive oxygen species is a major source of DNA damage. One of the oxidation lesions formed, 5-hydroxy-2′-deoxycytidine, has been shown to miscode by some replicative DNA polymerases but not by error VE-821 molecular weight prone polymerases capable of translesion synthesis. The 5-hydroxy-2′-deoxycytidine lesion is repaired by DNA. glycosylases that require the 5-hydroxycytidine base to be extrahelical so it can enter into the enzyme’s active site where it is excised off the DNA backbone to afford an abasic site. The thermodynamic and nuclear magnetic resonance results presented here describe the effect of a 5-hydroxy-2′-deoxycytidine center dot 2′-deoxyguanosine base pair on the stability of two different: DNA duplexes. The results demonstrate that the lesion is highly destabilizing and that the energy barrier for the unstacking of 5-hydroxy-2′-deoxycytidine from the DNA duplex may be low. This could provide a thermodynamic mode of adduct identification by DNA glycosylases that requires the lesion to be extrahelical.”
“The objective of this work was to examine immediate physiological plant responses to hail and subsequent recovery in terms of evapotranspiration, leaf temperature and primary photochemical processes using apple as a model crop.

Non-haematologic grade 3/4 toxicities included fatigue, condition aggravated, hypokalaemia, tumour pain, acneiform dermatitis, diarrhoea, hyperbilirubinaemia and pulmonary haemorrhage, in one patient each. Of 25 patients evaluable for tumour response, 2 patients had partial response and 20 patients had stable disease.

The recommended doses for oral vinflunine and erlotinib combination were, respectively, 115 mg/day from day 1 to day 5 and from day 8 to day 12 every 3 weeks and 150 mg/day. There was no mutual impact on pharmacokinetics. The combination was safe but evaluation in phase II is needed to further refine the activity and Ricolinostat cost toxicity that can Salubrinal cost be expected

with prolonged administration of this dose schedule.”
“Background: Increasing evidence indicates that brain kappa-opioid receptors (KORs) are involved in regulation of mood states. In animal models often used to study psychiatric illness, KOR agonists produce depressive-like effects (e.g., anhedonia), whereas KOR antagonists produce antidepressant- and anxiolytic-like effects. The ability of KOR agonists to produce anhedonia-like signs in laboratory animals raises the possibility that this class of drugs might be useful to ameliorate states characterized by excess reward or motivation, such as mania or stimulant intoxication.\n\nMethods: We examined how the selective KOR agonist U69,593 affects cocaine-induced facilitation of intracranial self-stimulation (ICSS), a model of the abnormally increased reward function that characterizes mania and stimulant intoxication. Rats with stimulating electrodes implanted in the medial forebrain bundle (MFB) were tested with intraperitoneal injections of U69,593 (.063-.5 mg/kg) alone, cocaine (1.25-10 mg/kg) alone, and combinations of the drugs.\n\nResults: Cocaine dose-dependently decreased ICSS thresholds, indicating that it enhanced the LEE011 rewarding

impact of MFB stimulation. In contrast, U69,593 dose-dependently increased ICSS thresholds, indicating that it decreased the rewarding impact of the stimulation. Pretreatment with U69,593 blocked cocaine-induced decreases in ICSS thresholds at doses that had negligible effects on their own.\n\nConclusions: Activation of KORs reduces the reward-related effects of cocaine. Inasmuch as cocaine-induced behavioral stimulation in rodents may model key aspects of enhanced mood in humans, these findings raise the possibility that KOR agonists might ameliorate symptoms of conditions characterized by increased motivation and hyperfunction of brain reward systems, such as mania and stimulant intoxication.

Control group participants were directed to static AZD8055 cost Web pages providing general information about cholesterol management.\n\nResults: The primary outcome was the proportion of participants that commenced or increased use of prescribed cholesterol-lowering therapy. Of the total 2099 randomized participants, 304 (14%) met eligibility criteria for cholesterol-lowering therapy but were not prescribed treatment, and 254 (12%) were prescribed treatment but were not achieving the recommended target level. Treatment was commenced or increased in 64 (6.0%) of the 1062 intervention group participants and 79 (7.6%) of the

1037 control group participants (% difference = -1.6%, 95% confidence interval [CI] -3.75 to 0.57, P = .15). No differences were found between the randomized groups for the secondary outcomes of “discussed treatment with a health professional” (% difference = -3.8%, 95% confidence interval [CI] -8.16 to 0.19, P = .08), “had their cholesterol JQ-EZ-05 research buy checked” (% difference = -1.5%, 95% CI -5.79 to 2.71, P = .48), “had their blood pressure checked” (% difference = 1.4%, 95% CI -2.55 to 5.34, P = .49) or made a lifestyle change (P values between .49 and .96).\n\nConclusions: Despite providing specific carefully tailored advice, this website had no detectable effect on cholesterol management strategies. This finding

raises considerable uncertainty about the value of Internet-based tools providing tailored advice directly to consumers.\n\nTrial Registration: NCT00220974; http://clinicaltrials.gov/ct2/show/NCT00220974 (Archived by WebCite at http://www.webcitation.org/5sdq63rrY)”
“The

review presents the latest evidence on the calcium antagonist amlodipine, summarizing its mechanisms of action, its pleiotropic, endothelial function-related effects, and its anti-atherogenic activity. Amlodipine suppresses the proliferation of vascular smooth myocytes and extracellular matrix and improves endothelial vasodilatation, despite the absence of L-type calcium channels in these cells. This mechanism is related JPH203 concentration to an increase in endothelial nitric oxide (NO) release. The results of experimental studies on the role of S and R amlodipine isomers in its hemodynamic and pleiotropic activity are presented. While S-amlodipine is a pharmacologically active blocker of L-type calcium channels, R-amlodipine increases endothelial NO release. New medications have been developed, based on S-amlodipine. It has been shown that S-amlodipine 5 mg/d is bioequivalent to amlodipine 10 mg/d. The pharmacodynamics analysis demonstrated that S-amlodipine 5 mg/d and amlodipine 10 mg/d did not differ significantly in terms of mean levels of systolic and diastolic blood pressure, or mean heart rate. S-amlodipine was better tolerated and characterised by a lower incidence of peripheral edema than amlodipine.

Membrane binding of a single M domain is sufficient to fully activate the enzymatic activity of the CCT dimer while sustaining the low affinity, reversible membrane interaction required for regulation of CCT activity.”
“Calcium- and voltage-activated potassium channels (BK) are regulated by a multiplicity of signals. The prevailing view is that different BK gating mechanisms converge to determine channel opening and that these gating

mechanisms are allosterically coupled. In most instances the pore forming alpha subunit of BK is associated with one of four alternative beta subunits that appear to target specific gating mechanisms to regulate the channel activity. In particular, click here beta 1 stabilizes the active configuration of the

BK voltage sensor having a large effect on BK Ca2+ sensitivity. To determine the extent to which beta subunits regulate the BK voltage sensor, we measured gating currents induced by the pore-forming BK alpha subunit alone and with the different beta subunits expressed in Xenopus oocytes (beta 1, beta 2IR, beta 3b, and beta 4). We found that beta 1, beta 2, and beta 4 stabilize the BK voltage sensor in the active conformation. beta 3 has no effect on voltage sensor equilibrium. In addition, beta 4 decreases the apparent number of charges per voltage sensor. CSF-1R inhibitor The decrease in the charge associated with the voltage sensor in alpha beta 4 channels explains most of their biophysical properties. For channels composed of the

alpha subunit alone, gating charge increases slowly with pulse duration as expected if a significant fraction of this charge develops with a time course comparable to that of K+ current activation. In the presence of beta 1, beta 2, and beta 4 this slow component develops in advance of and much more rapidly than ion current activation, suggesting that BK channel opening proceeds in two steps.”
“Estimating survival and documenting causes and timing of mortality events in neonate bighorn sheep (Ovis canadensis) improves understanding of population ecology and factors influencing recruitment. During 2010-2012, we captured and radiocollared 74 neonates in the Black Hills, South Dakota, of which 95% (70) died before 52 weeks of age. Pneumonia (36%) was the leading cause of mortality learn more followed by predation (30%). We used known fate analysis in Program MARK to estimate weekly survival rates and investigate the influence of intrinsic variables on 52-week survival. Model S-1 wk,S- 2-8 wks,S- >8 wks had the lowest AIC(c) (Akaike’s Information Criterion corrected for small sample size) value, indicating that age (3-stage age-interval: 1 week, 2-8 weeks, and >8 weeks) best explained survival. Weekly survival estimates for 1 week, 2-8 weeks, and >8 weeks were 0.81 (95% CI = 0.70-0.88), 0.86 (95% CI = 0.81-0.90), and 0.94 (95% CI = 0.91-0.96), respectively. Overall probability of surviving 52 weeks was 0.02 (95% CI = 0.01-0.07).

\n\nMaterials and Methods: In vitro investigation of angiogenesis was conducted utilizing HUVEC cells in Matrigel. Endothelial tubule formation assays were divided into four groups: Control, Radiated, Radiated + Low-Dose Rabusertib ic50 DFO and Radiated + High-Dose DFO. Tubule formation was quantified microscopically and video recorded for the four groups simultaneously during the experiment.

In vivo, three groups of Sprague-Dawley rats underwent external fixator placement and fracture osteotomy of the left mandible. Two groups received pre-operative fractionated radiotherapy, and one of these groups was treated with DFO after fracture repair. After 40 days, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics.\n\nResults: In vitro, endothelial EPZ-6438 chemical structure tubule formation assays demonstrated that DFO mitigated the deleterious effects of radiation on angiogenesis. Further, high-dose DFO cultures appeared to organize within 2 h of incubation and achieved a robust network that was visibly superior to all other experimental groups in an accelerated fashion. In vivo, animals subjected to a human equivalent dose of radiotherapy (HEDR) and left mandibular fracture demonstrated quantifiably diminished mu CT metrics of vascular density, as well as a 75% incidence of associated non-unions. The addition of

DFO in this setting markedly improved EVP4593 vascularity as demonstrated with 3D angiographic modeling. In addition, we observed an increased incidence of bony unions in the DFO treated group when compared to radiated fractures without treatment (67% vs. 25% respectively).\n\nConclusion: Our data suggest that selectively targeting angiogenesis with localized DFO injections is sufficient to remediate the associated severe vascular diminution resulting from a HEDR. Perhaps the most consequential and clinically relevant finding was the ability to reduce the incidence of non-unions in a model

where fracture healing was not routinely observed. (C) 2012 Elsevier Inc. All rights reserved.”
“We recently identified LY2033298 as a novel allosteric potentiator of acetylcholine (ACh) at the M-4 muscarinic acetylcholine receptor (mAChR). This study characterized the molecular mode of action of this modulator in both recombinant and native systems. Radioligand-binding studies revealed that LY2033298 displayed a preference for the active state of the M-4 mAChR, manifested as a potentiation in the binding affinity of ACh (but not antagonists) and an increase in the proportion of high-affinity agonist-receptor complexes. This property accounted for the robust allosteric agonism displayed by the modulator in recombinant cells in assays of [S-35]GTP gamma S binding, extracellular regulated kinase 1/2 phosphorylation, glycogen synthase kinase 3 beta phosphorylation, and receptor internalization.

Among these technologies, transcription activator-like effectors (TALE) has turned out to be one of the most versatile and incredibly robust platform for generating targeted molecular tools as demonstrated by fusion to various domains such as transcription activator, repressor and nucleases. Results: In this study, we

generated a novel nuclease architecture based on the transcription activator-like effector scaffold. In contrast to the existing Tail to Tail (TtT) and head to Head (HtH) nuclease architectures based on the symmetrical association of two TALE DNA binding domains fused to the C-terminal (TtT) or N-terminal (HtH) end of FokI, this novel architecture consists of LY333531 molecular weight the asymmetrical association VX-809 in vitro of two different engineered TALE DNA binding domains fused to the N- and C-terminal ends of FokI (TALE:: FokI and FokI:: TALE scaffolds respectively). The characterization of this novel Tail to Head (TtH) architecture in yeast enabled us to demonstrate its nuclease activity

and define its optimal target configuration. We further showed that this architecture was able to promote substantial level of targeted mutagenesis at three endogenous loci present in two different mammalian cell lines. Conclusion: Our results demonstrated that this novel functional TtH architecture which requires binding to only one DNA strand of a given endogenous locus has the potential to extend the targeting possibility of FokI-based TALE nucleases.”
“The success of a social group is often driven by its collective characteristics and the traits of its individuals. Thus, understanding how collective behavior is influenced by the behavioral composition of group members is an important first step to understand the ecology of collective personalities. Here, we investigated how the efficiency of several group behaviors is influenced by the aggressiveness of its members in two species FG 4592 of Temnothorax ants. In our manipulation of group composition, we created two experimentally

reconstituted groups in a split-colony design, i.e., each colony was split into an aggressive and a docile group of equal sizes. We found strong species-specific differences in how collective behaviors were influenced by its group members. In Temnothorax longispinosus, having more aggressive individuals improved colony defense and nest relocation efficiency. In addition, source colony identity strongly influenced group behavior in T. longispinosus, highlighting that manipulations of group compositions must control for the origin of the chosen individuals. In contrast, group composition and source colony did not influence collective behaviors in Temnothorax curvispinosus. This suggests that the mechanisms regulating collective behaviors via individual differences in behavior might differ among even closely related species.

Odds ratio indicated that heterozygosity of genotypes -819 CT and -592 AC was more strongly associated with liver chronicity. Significantly, AA homozygous genotype was dominant in chronic hepatitis B cases in IFN-gamma + 874 and IL-10 (-1082 and -592) and is

associated with increased risk of persistent infection.”
“Hippocampal theta rhythm arises from a combination of recently described intrinsic theta oscillators and inputs from multiple brain areas. Interneurons expressing the markers parvalbumin (PV) and somatostatin (SOM) are leading candidates to participate in intrinsic rhythm generation and principal cell (PC) coordination in distal CA1 and subiculum. We tested their involvement by optogenetically activating and silencing PV or SOM interneurons in an intact hippocampus preparation that preserves intrinsic Pevonedistat research buy connections and oscillates spontaneously at theta frequencies. Despite evidence suggesting that SOM interneurons are crucial for theta, optogenetic manipulation of these interneurons modestly influenced theta rhythm. However, SOM

interneurons were able to strongly modulate temporoammonic inputs. In contrast, activation of PV interneurons powerfully controlled PC network and rhythm generation optimally at 8 Hz, while continuously silencing them disrupted theta. Our results thus demonstrate a pivotal role of PV but not SOM interneurons for PC synchronization and the emergence of intrinsic hippocampal theta.”
“Bacterial populations frequently act as a collective by secreting a wide Selleckchem PCI32765 range of compounds necessary for cell-cell communication, host colonization and virulence. How such behaviours avoid exploitation by spontaneous ‘cheater’ mutants that use but do not contribute to secretions

remains unclear. We investigate this question using Pseudomonas aeruginosa swarming, a collective surface motility requiring massive secretions of rhamnolipid biosurfactants. We first show that swarming is immune to the evolution of Small molecule library rhlA-’cheaters’. We then demonstrate that P. aeruginosa resists cheating through metabolic prudence: wild-type cells secrete biosurfactants only when the cost of their production and impact on individual fitness is low, therefore preventing non-secreting strains from gaining an evolutionary advantage. Metabolic prudence works because the carbon-rich biosurfactants are only produced when growth is limited by another growth limiting nutrient, the nitrogen source. By genetically manipulating a strain to produce the biosurfactants constitutively we show that swarming becomes cheatable: a non-producing strain rapidly outcompetes and replaces this obligate cooperator. We argue that metabolic prudence, which may first evolve as a direct response to cheating or simply to optimize growth, can explain the maintenance of massive secretions in many bacteria. More generally, prudent regulation is a mechanism to stabilize cooperation.

The degradation of aggrecan by upregulated disintegrin and

metalloproteinase with trombospondin motifs (ADAMTSs) is the key event in the development of both rheumatoid arthritis (RA) and osteoarthritis (OA). Increased levels of leptin in both RA and OA have been demonstrated, thus linking leptin to arthritic diseases, but the mechanism has not been clarified. This study investigated the putative role of signaling pathways (p38, JNK, MEK1, NF-?B, and PI3) involved in leptin-induced cartilage destruction. Normal human articular chondrocytes were cultured with recombinant human leptin at 100, 250, 500, and 1000ng/mL doses for 6, 12, 24, and 48h, after which ADAMTS-4, -5, and -9 genes expression were GSI-IX determined by real time-polymerase chain reaction (RT-PCR) and Western Blot methods. The signaling pathways involved in leptin-induced ADAMTSs upregulation were also investigated by using inhibitors of signaling pathways. It was demonstrated that ADAMTSs expression level was peaked at 1000ng/mL doses for 48hours,

and MAPKs (p38, JNK, and MEK) and NF-?B signaling pathways involving in leptin triggered ADAMTSs upregulation. Obesity as a risk for RA and OA may contribute to the inflammation of both RA and OA diseases by secreting adipokines VX-661 chemical structure like leptin. We hypothesize that leptin is involved in the development of RA and OA accompanied with obesity by increasing ADAMTS-4, -5, and -9 genes expression via MAPKs and NF-?B signaling pathways.”
“Burkholderia pseudomallei is a select agent and the causative agent of melioidosis. Variations in previously reported chlorine and monochloramine concentration time (Ct) values for disinfection of this organism make decisions regarding the appropriate levels of chlorine in water treatment systems difficult. This study identified the variation in Ct values for 2-, 3-, and 4-log(10) reductions of eight environmental and clinical isolates of B. pseudomallei in phosphate-buffered water. The greatest calculated Ct values for a 4-log(10) inactivation were 7.8 mg.min/liter for free available chlorine (FAC) at pH 8 and

5 degrees C and 550 mg.min/liter for monochloramine at pH 8 and 5 C. Ionic strength of test solutions, culture hold times in water, and cell washing were ruled out as sources of the differences AZD1480 clinical trial in prior observations. Tolerance to FAC was correlated with the relative amount of extracellular material produced by each isolate. Solid-phase cytometry analysis using an esterase-cleaved fluorochrome assay detected a 2-log(10)-higher level of organisms based upon metabolic activity than did culture, which in some cases increased Ct values by fivefold. Despite strain-to-strain variations in Ct values of 17-fold for FAC and 2.5-fold for monochloramine, standard FAC disinfection practices utilized in the United States should disinfect planktonic populations of these B. pseudomallei strains by 4 orders of magnitude in less than 10 min at the tested temperatures and pH levels.

The IH progressed rapidly, and gestational hypertension was observed in the 36th week. The lesions did not subside, despite treatment with corticosteroids and phototherapy. She delivered a healthy male baby via cesarean section in the 37th week. One month after her delivery, her skin returned to normal, except for residual pigmentation, with complete recovery 3 months postpartum. Conclusion: An experienced medical team comprising obstetricians,

dermatologists, perinatologists and neonatologists is critical to aggressively treat this life-threatening check details specific dermatosis of pregnancy and to prevent ensuing complications, such as fluid and electrolyte imbalance, secondary infection and placental insufficiency. Copyright (C) 2011 S. Karger AG, Basel”
“Objective: To compare the effect

of two lipid emulsions on Compound C cost the development of retinopathy of prematurity in very low birth weight infants.\n\nDesign: Randomized controlled study.\n\nPatients and methods: Eighty very low birth weight infants receiving parenteral nutrition from the first day of life were evaluated. One of the two lipid emulsions were used in the study infants: Group 1 (n = 40) received fish-oil based lipid emulsion (SmofLipid(R)) and Group 2 (n = 40) soybean oil based lipid emulsion (Intralipid(R)).\n\nMain outcome measures: The development of retinopathy of prematurity and the need for laser photocoagulation were assessed.\n\nResults: The maternal and perinatal characteristics were similar in both groups. The median (range) duration of parenteral nutrition [14 days (10-28) vs 14(10-21)] and hospitalization [34 days (20-64) BIIB057 solubility dmso vs 34 (21-53)] did not differ between the groups. Laboratory data including complete blood count, triglyceride level, liver and kidney function tests recorded before and after parenteral nutrition also did not differ between the two groups. In Group 1, two patients (5.0%) and in Group 2,13 patients (32.5%) were diagnosed with retinopathy

of prematurity (OR: 9.1,95% Cl 1.9-43.8, p = 0.004). One patient in each group needed laser photocoagulation, without significant difference. Multivariate analysis showed that only receiving fish-oil emulsion in parenteral nutrition decreased the risk of development of retinopathy of prematurity [OR: 0.76, 95% Cl (0.06-0.911), p = 0.04].\n\nConclusions: Premature infants with very low birth weight receiving an intravenous fat emulsion containing fish oil developed less retinopathy of prematurity. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Objective: To describe the prognostic factors and outcomes of adults with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system.