Radiosynthesis and preliminary biological evaluation of a new (18)F-labeled triethylene glycol derivative of triphenylphosphonium.

Delocalized lipophilic cations such as [(18)F]fluorobenzyltriphenylphosphonium ([(18)F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [(18)F]FBnTP synthesis using triphenylphosphine hydrobromide (PPh3 •HBr) without preparing an intermediate that contains benzyl bromide structure. Applying this new method, we synthesized and evaluated a novel (18)F-labeled PEGylated BnTP derivative ([(18)F]FPEGBnTP). In vitro cellular uptake study demonstrated that [(18)F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart : liver uptake ratio of [(18)F]FPEGBnTP (4.00 at 60 min) was superior to that of [(18)F]FBnTP (1.50 at 60 min). However, [(18)F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120-min post-injection. These results imply the possibility of [(18)F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow-dependent uptake study.

Effect of multi-strain bifidobacteria supplementation on intestinal microbiota development in low birth weight neonates: a randomized controlled trial.

Single-strain Bifidobacterium species are commonly used as probiotics with low birth weight neonates. However, the effectiveness and safety of multi-strain Bifidobacterium supplementation are not well known. Thirty-six neonates weighing less than 2,000 g (558-1,943 g) at birth and admitted to a neonatal intensive care unit were randomly assigned to receive a single strain or triple strains of Bifidobacterium with lactulose enterally for 4 weeks from birth. The relative abundances of Staphylococcus and Bifidobacterium in the fecal microbiota at weeks 1, 2, and 4 were investigated. Based on the study results, no significant difference was detected between the two groups in the abundance of Staphylococcus; however, the triple-strain group had significantly high abundances of Bifidobacterium at weeks 2 and 4. The fecal microbiota in the triple-strain group had significantly lower alpha diversity (Bifidobacterium-enriching) after week 4 and was different from that in the single-strain group, which showed a higher abundance of Clostridium. No severe adverse events occurred in either group during the study period. Although no significant difference was detected between single- and multi-strain bifidobacteria supplementation in the colonization of Staphylococcus in the fecal microbiota of the neonates, multi-strain bifidobacteria supplementation contributed toward early enrichment of the microbiota with bifidobacteria and suppression of other pathogenic bacteria, such as Clostridium spp.

Beyond 2D: A scalable and highly sensitive method for a comprehensive 3D analysis of kidney biopsy tissue.

The spatial organization of various cell populations is critical for the major physiological and pathological processes in the kidneys. Most evaluation of these processes typically comes from a conventional 2D tissue cross-section, visualizing a limited amount of cell organization. Therefore, the 2D analysis of kidney biopsy introduces selection bias. The 2D analysis potentially omits key pathological findings outside a 1- to 10-µm thin-sectioned area and lacks information on tissue organization, especially in a particular irregular structure such as crescentic glomeruli. In this study, we introduce an easy-to-use and scalable method for obtaining high-quality images of molecules of interest in a large tissue volume, enabling a comprehensive evaluation of the 3D organization and cellular composition of kidney tissue, especially the glomerular structure. We show that CUBIC and ScaleS clearing protocols could allow a 3D analysis of the kidney tissues in human and animal models of kidney disease. We also demonstrate that the paraffin-embedded human biopsy specimens previously examined via 2D evaluation could be applicable to 3D analysis, showing a potential utilization of this method in kidney biopsy tissue collected in the past. In summary, the 3D analysis of kidney biopsy provides a more comprehensive analysis and a minimized selection bias than 2D tissue analysis. Additionally, this method enables a quantitative evaluation of particular kidney structures and their surrounding tissues, with the potential utilization from basic science investigation to applied diagnostics in nephrology.

[Sustained molecular remission with a tyrosine kinase inhibitor alone for seven months in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia].

Herein, we report the case of a 28-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). The patient received induction chemotherapy, including imatinib (IM) therapy, which required early cessation because of a severe infection. After the resolution of the infection, general flaccid paralysis was observed, which was diagnosed as critical illness myopathy (CIM). Ph(+)ALL showed molecular remission (MR) on day 42. We intended to maintain MR with only IM therapy for several months until the improvement of CIM; however, owing to the patient's intolerance to IM, therapy was changed to dasatinib. Because the symptoms of myopathy gradually improved and disappeared completely, the patient was able to undergo one course of intensive chemotherapy and allogeneic stem cell transplantation from an HLA-matched sibling donor, 8 months after admission (7 months after the re-administration of IM). Thus, this case report suggests that a tyrosine kinase inhibitor is an alternative therapy for maintaining the response of Ph(+)ALL patients who refrain from conventional chemotherapy.

Maternal magnesium sulfate administration increases early-onset hyperkalemia risk in premature infants: A propensity score-matched, case-control study.

BACKGROUND: Magnesium sulfate (MgSO4) is a common substance administered to pregnant women with preeclampsia or eclampsia to prevent and treat seizures or gestational hypertension. This study aimed to evaluate whether administering maternal magnesium sulfate increased the risk of early-onset hyperkalemia in preterm infants. METHODS: This single-center, propensity score-matched, case-control study examined preterm infants born within 24-36 weeks of gestation using electronic medical records between January 2015 and June 2019, in the Saitama City Hospital, Japan. We categorized infants according to their maternal MgSO4 administration status. After adjusting for perinatal information and maternal treatment, we compared the incidence of the variables, including neonatal hyperkalemia, within 24 h after birth between the matched cohorts. All infants in Model 1 were analyzed separately, while in Model 2 infants with birth weight of less than 1000 g were excluded. RESULTS: We enrolled 421 infants (maternal MgSO4 group, 124; control group, 297). Ninety-five infants in Model 1 and 86 in Model 2 were matched in each group using propensity scores, respectively. In the matched cohorts of both models, infants in the maternal MgSO4 group had a higher hyperkalemia incidence than did those in the control group (42.1% vs. 7.4% in Model 1, 44.2% vs. 5.8% in Model 2, respectively; p < 0.0001). However, there was no relationship between the duration of intrauterine exposure to MgSO4 and early-onset neonatal hyperkalemia incidence. CONCLUSION: Our study demonstrated that maternal MgSO4 administration, even for a short period of time, may increase the risk of early-onset hyperkalemia in preterm infants. Accordingly, physicians should be cautious when administering serum potassium to infants born to mothers administered MgSO4, especially within 24 h after birth.

Fibroblast growth factor 23 levels in cord and peripheral blood during early neonatal period as possible predictors of affected offspring of X-linked hypophosphatemic rickets: report of three female cases from two pedigrees.

OBJECTIVES: The role of serum fibroblast growth factor 23 (FGF23) level in early neonatal period on the diagnosis of X-linked hypophosphatemic rickets (XLH) remains unclear. CASE PRESENTATION: Two female patients from the first pedigree had an affected mother, and the other female from the second pedigree had an affected father. In all three cases, FGF23 levels were high in cord blood and peripheral blood at day 4-5. Additionally, the FGF23 levels considerably increased from birth to day 4-5. We identified a PHEX pathogenic variant and initiated treatment during infancy in each case. CONCLUSIONS: In neonates with a parent diagnosed as PHEX-associated XLH, FGF23 in cord blood and peripheral blood at day 4-5 may be useful markers for predicting the presence of XLH.

Transient hypercalcemia followed by hypocalcemia in a preterm infant after maternal magnesium sulfate therapy.

Maternal use of magnesium sulfate has been associated with neonatal hypocalcemia and bone changes. We report the case of a preterm male infant who presented hypercalcemia before developing hypocalcemia after maternal magnesium sulfate therapy. Magnesium sulfate was used for premature rupture of membranes for 32 days, and the patient was delivered at 33 weeks gestation. The cord blood showed ionized calcium 1.54 mmol/L. His serum calcium and magnesium were 11.4 mg/dL and 3.5 mg/dL after birth and fell to 6.6 mg/dL and 2.7 mg/dL at 6 hours, respectively. The intact parathyroid hormone level was 18 pg/mL at 6 h. Radiography showed transverse radiolucent metaphyseal bands of the proximal humerus bone, suggesting disturbance in normal ossification. Transient hypercalcemia before the development of hypocalcemia after maternal magnesium sulfate therapy has not been previously reported. We speculate that maternal long-term magnesium sulfate therapy led to defective ossification and transient hypercalcemia in the offspring. Subsequent hypocalcemia was thought to be due to the inhibition of parathyroid hormone secretion by hypercalcemia and hypermagnesemia.

Influence of magnesium chloride on the dose-response of polyacrylamide-type gel dosimeters.

We investigated the effect of magnesium chloride (MgCl2) on the nuclear magnetic resonance dose-response of polyacrylamide-type (PAGAT, NIPAM, and VIPET) gel dosimeters containing acrylamide, N-isopropylacrylamide, and N-vinylpyrrolidone as a monomer, respectively. The dose-transverse relaxation rates (1/T2 = R2) obtained from magnetic resonance imaging data revealed that a substantial increase in the dose-R2 response occurred as the concentration of MgCl2 in the gel dosimeters increased. The sensitivity of the PAGAT gel with 1.0 M MgCl2 was found to be approximately one order higher than that of the same gel without MgCl2. In addition, the water equivalences of the gels with MgCl2 were evaluated over a wide range of photon energies. The results indicated that MgCl2 acts as a powerful sensitizer to radiation-induced free-radical polymerization in polyacrylamide-type gel dosimeters, but does not interfere with the desirable properties of basic polyacrylamide-type gel dosimeters (i.e., the dose rate and dose integration).

Transient Fanconi syndrome in two preterm infants with hydronephrosis and urinary tract infection.

Type IV renal tubular acidosis is known to occur in obstructive uropathy with urinary tract infection. Fanconi syndrome, however, has not been described in these settings. We report two preterm infants who developed Fanconi syndrome associated with hydronephrosis and urinary tract infection. Patient 1 is a boy with 21 trisomy, bilateral renal hypoplasia and bilateral vesicoureteral reflux delivered at 35 weeks' gestation. At postnatal day 42, he developed Fanconi syndrome after urinary tract infection, which persisted until the surgical correction of vesicoureteral reflux. Patient 2 was delivered at 35 weeks' gestation. At postnatal day 9, he was admitted for severe dehydration. He had phimosis and ultrasonography showed left pelviectasis. Laboratory data were compatible with Fanconi syndrome, which resolved spontaneously after fluid therapy. Subsequently urine culture grew bacteria and treatment for infection and topical corticosteroid for phimosis were performed. DMSA scintigraphy performed later showed left renal scar. Tubular cell stretch, due to vesicoureteral reflux in Patient 1 and phimosis in Patient 2, and urinary tract infection in association with immaturity of tubules are thought to have caused Fanconi syndrome.

[Examination of bed overlaps in 18F-FDG PET/CT 3D data acquisition].

The purpose of this study was to determine the best bed overlaps in PET/CT 3D acquisition to reconstruct a transverse image with uniform quality not depending on axial slice position. First, the value of the image contrast ratio, non-uniformity (NU) value, and coefficient of variation (COV) were examined in the image of a cylindrical phantom at each slice position. The image-contrast ratio was almost constant in all slice images, and the NU value and COV were also constant in the slice images up to 13 and 19 slices from the center, respectively, but these values increased with closeness to the edge of the detector. Secondly, COV and image contrast ratios at different sizes of (18)F-FDG concentration (phi 19 mm, phi 16 mm, phi 13 mm, phi 10 mm) were examined in the case of overlapping the bed frame with 11, 15, and 21 slices in acquiring data in 3D mode. In 21 and 15 slices overlapping in acquisition, the image contrast ratios for all concentrations were greater than 0.13, which was the threshold image contrast ratio needed to identify FDG concentration from the background image with naked eye scanning under our conditions. However, in 11 slices with overlapping acquisition, the image-contrast ratio for a phi 10 mm concentration were close to or less than 0.13 in the all slice images. As a result, 15 overlapping slices was a reasonable minimum number of slices to identify a phi 10 mm (18)F-FDG concentration while maintaining the image quality in PET/CT 3D acquisition in our institution.

[Polymer gel dosimetry--the dose response for X-ray irradiation].

Polymer gel dosimetry has been considered a promising technique for clinical use, but this potential has not yet been fully realized in Japan. One reason may be because the commercialized gel detector, BANG gel, is expensive and it is only produced abroad. A second reason is the difficulty of controlling dose sensitivity of the gel so that it is stable under ordinary clinical conditions. In this work we introduce two types of gel detectors (MAG and PAG) which we produced in-house. First the method of fabrication of gel is presented in detail, then the dose responses of MAG and PAG for X-ray irradiation are evaluating for MRI and X-ray CT scanning. The MAG-type gel is useful in low contrast dosimetry because of the high sensitivity in its dose response (R2). The PAG-type gel is effective for dosimetry in multiple field irradiations because its dose response (CT value) has reproducibility independent of the different irradiation conditions. Finally, we summarize the potential for clinical use of polymer gel dosimetry with these gel detectors.

[Comparison evaluation of polymer gel with a water phantom.].

We have investigated the properties of three polymergels: G gel, A gel, and C gel. These polymer gels changed only the chemical reagent for the gel. The water equivalence was determined by comparing the polymer gels macroscopic photon and electron interaction cross sections over the energy range from 10 KeV to 50 MeV and by Monte Carlo modeling of percentage depth doses. Polymer gels have a chemical reagent for the gel and monomer concentration and therefore their mass density is up to 1.70-2.91 % higher than water. This results in differences between the cross section ratios of the polymer gels and water of up to 0.01-3.00 % for the attenuation coefficients ratio and relative stopping power throughout the energy range. Monte Carlo modeling was done for the polymer gels to model the electron and photon transport resulting from a 6 MV photon beam. The absolute percentage differences between each gel and water were within 1 % of the relative percentage differences. The results showed that the A gel formulation had the most suitable water equivalence of the polymer gels investigated due to its lower mass density measurement compared with G gel and C gel.