Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

A severe complication in the replacement therapy of hemophilia A (HA) patients is the development of alloantibodies (inhibitors) against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in the regulation of B-lymphocyte development are other possible targets as genetic risk factors. This study assesses the possible involvement of 9 selected single nucleotide gene polymorphisms (SNPs) with interleukins (IL-4, IL-5, and IL-10), transforming growth factor beta 1 (TGF-β1), and interferon gamma (IFN-γ) in inhibitor development in severely affected HA patients carrying a null mutation in the F8 gene.', 'A total of 173 HA patients were screened for intron 22 inversion and null mutations (nonsense and deletions). Genotyping of a total of 9 SNPs in genes IL-4, IL-5, IL-10, TGF-β1, and IFN-γ in 103 patients and 100 healthy individuals was carried out.', 'An association analysis between 42 inhibitor (+) and 61 inhibitor (-) patients showed a significant association with the T allele of rs2069812 in the IL-5 gene promoter and patients with inhibitors (p=0.0251). The TT genotype was also significantly associated with this group with a p-value of 0.0082, odds ratio of about 7, and confidence interval of over 90%, suggesting that it is the recessive susceptibility allele and that the C allele is the dominant protective allele.
Is a Polymorphism in the IL-5 Gene Associated with Inhibitor Development in Severe Hemophilia A Patients?

Hyponatraemia is a common, potentially life-threatening, complication of thiazide diuretics. The mechanism of thiazide-induced hyponatraemia is incompletely understood. Previous experiments have suggested a direct effect of thiazide diuretics on the plasma membrane expression of aquaporin (AQP)2.', 'We examined the effects of a single re-exposure to hydrochlorothiazide (HCTZ) 50\u200amg on water balance, renal sodium handling and osmoregulation in 15 elderly hypertensive patients with a history of thiazide-induced hyponatraemia and 15 matched hypertensive controls using thiazide diuretics without previous hyponatraemia.', 'Patients with thiazide-induced hyponatraemia had significantly lower body weight and lower plasma sodium and osmolality at baseline. After HCTZ administration, plasma sodium and osmolality significantly decreased and remained lower in patients compared with controls (P\u200a<\u200a0.001). Plasma antidiuretic hormone (ADH) and urine AQP2 were low or suppressed in patients, whereas solute and electrolyte-free water clearance was significantly increased compared with controls. Ad libitum water intake was significantly higher in patients (2543\u200a±\u200a925\u200aml) than in controls (1828\u200a±\u200a624\u200aml, P\u200a<\u200a0.05), whereas urinary sodium excretion did not differ. In contrast, urea excretion remained significantly lower in patients (263\u200a±\u200a69\u200ammol per 24\u200ah) compared with controls (333\u200a±\u200a97\u200ammol per 24\u200ah, P\u200a<\u200a0.05) and predicted the decrease in plasma sodium following HCTZ administration.
Is thiazide-induced hyponatraemia associated with increased water intake and impaired urea-mediated water excretion at low plasma antidiuretic hormone and urine aquaporin-2?

Cerebral pressure passivity (CPP) in sick newborns can be detected by evaluating coupling between mean arterial pressure (MAP) and cerebral blood flow measured by near infra-red spectroscopy hemoglobin difference (HbD). However, continuous MAP monitoring requires invasive catheterization with its inherent risks. We tested whether heart rate (HR) could serve as a reliable surrogate for MAP in the detection of CPP in sick newborns.', 'Continuous measurements of MAP, HR, and HbD were made and partitioned into 10-min epochs. Spectral coherence (COH) was computed between MAP and HbD (COHMAP-HbD) to detect CPP, between HR and HbD (COHHR-HbD) for comparison, and between MAP and HR (COHMAP-HR) to quantify baroreflex function (BRF). The agreement between COHMAP-HbD and COHHR-HbD was assessed using ROC analysis.', 'We found poor agreement between COHMAP-HbD and COHHR-HbD in left hemisphere (area under the ROC curve (AUC) 0.68) and right hemisphere (AUC 0.71). Baroreflex failure (COHMAP-HR not significant) was present in 79% of epochs. Confining comparison to epochs with intact BRF showed an AUC of 0.85 for both hemispheres.

Does baroreflex dysfunction in sick newborns make heart rate an unreliable surrogate for blood pressure changes?