Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.

Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients.

In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature.

The Role of Ureaplasma and Mycoplasma Species in Recurrent Lower Urinary Tract Infection in Females: A Scoping Review.

It is unknown if recurrent urinary tract infection in the gynecologic population is associated with Mycoplasma and Ureaplasma genitourinary infections. The purpose of this scoping review is to highlight the literature surrounding Mycoplasma and Ureaplasma infections in the setting of recurrent urinary tract infections in the gynecologic population. MEDLINE ALL and Embase were searched to retrieve articles published in or after 1950 through 2024. Studies included were those with adults over age 18, non-pregnant, diagnosed with recurrent urinary tract infection and concurrent genitourinary infection with Ureaplasma or Mycoplasma published in English. Study designs eligible were quantitative, qualitative, and mixed methods studies. Publication types were also extended to conference abstracts and unpublished data. 2 independent investigators systematically performed title/abstract screening and full-text review using standardized inclusion criteria. For disagreements in either title and abstracts or full-text articles, consensus was reached through discussion by the 2 screeners and/or a 3rd final adjudicator. Screening and data extraction were performed on Covidence, a web-based platform for systematic review management. There were 1170 studies identified before title and abstract screening. 26 full-text articles were reviewed for eligibility. Of these, 23 full-text studies were excluded. 3 studies met full inclusion criteria and data extraction was performed on these 3 studies. There were 2 additional studies included after identification via other methods. There is a need for more recent and robust studies examining the role of Ureaplasma and Mycoplasma genitourinary infections amongst gynecologic patients with recurrent urinary tract infections.

Role of cosyntropin in the management of postpartum post-dural puncture headache: a two-center retrospective cohort study.

BACKGROUND: Research suggests that postpartum post-dural puncture headache (PDPH) might be prevented or treated by administering intravenous cosyntropin. METHODS: In this retrospective cohort study, we questioned whether prophylactic (1 mg) and therapeutic (7 µg/kg) intravenous cosyntropin following unintentional dural puncture (UDP) was effective in decreasing the incidence of PDPH and therapeutic epidural blood patch (EBP) after birth. Two tertiary-care American university hospitals collected data from November 1999 to May 2017. Two hundred and fifty-three postpartum patients who experienced an UDP were analyzed. In one institution 32 patients were exposed to and 32 patients were not given prophylactic cosyntropin; in the other institution, once PDPH developed, 36 patients were given and 153 patients were not given therapeutic cosyntropin. The primary outcome for the prophylactic cosyntropin analysis was the incidence of PDPH and for the therapeutic cosyntropin analysis in exposed vs. unexposed patients, the receipt of an EBP. The secondary outcome for the prophylactic cosyntropin groups was the receipt of an EBP. RESULTS: In the prophylactic cosyntropin analysis no significant difference was found in the risk of PDPH between those exposed to cosyntropin (19/32, 59%) and unexposed patients (17/32, 53%; odds ratio (OR) 1.37, 95% CI 0.48 to 3.98, P = 0.56), or in the incidence of EBP between exposed (12/32, 38%) and unexposed patients (6/32, 19%; OR 2.6, 95% CI 0.83 to 8.13, P = 0.095). In the therapeutic cosyntropin analysis, in patients exposed to cosyntropin the incidence of EBP was significantly higher (20/36, 56% vs. 43/153, 28%; OR 3.20, 95% CI 1.52 to 6.74, P = 0.002). CONCLUSIONS: Our data show no benefits from the use of cosyntropin for preventing or treating postpartum PDPH.

NFKBIZ polymorphisms and susceptibility to pneumococcal disease in European and African populations.

The proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) has a central role in host defence against pneumococcal disease. Both rare mutations and common polymorphisms in the NFKBIA gene encoding the NF-kappaB inhibitor, IkappaB-alpha, associate with susceptibility to bacterial disease, but the possible role of polymorphisms within the related IkappaB-zeta gene NFKBIZ in the development of invasive pneumococcal disease (IPD) has not been reported previously. To investigate this further, we examined the frequencies of 22 single-nucleotide polymorphisms spanning NFKBIZ in two case-control studies, comprising UK Caucasian (n=1008) and Kenyan (n=723) individuals. Nine polymorphisms within a single UK linkage disequilibrium (LD) block and all four polymorphisms within the equivalent, shorter Kenyan LD block displayed either a significant association with IPD or a trend towards association. For each polymorphism, heterozygosity was associated with protection from IPD when compared with the combined homozygous states (for example, for rs600718, Mantel-Haenszel 2 x 2 chi(2)=7.576, P=0.006, odds ratio (OR)=0.67, 95% confidence interval (95% CI) for OR: 0.51-0.88; for rs616597, Mantel-Haenszel 2 x 2 chi(2)=8.715, P=0.003, OR=0.65, 95% CI: 0.49-0.86). We conclude that multiple NFKBIZ polymorphisms associate with susceptibility to IPD in humans. The study of multiple populations may aid in fine mapping of associations within extensive regions of strong LD ('transethnic mapping').

The ontogeny of antigen-specific T cells.

Although the fetal lamb is unable to form circulating antiovalbumin antibodies until about 120 days of gestation, ovalbumin-specific helper T cells can be stimulated to function at an earlier age. This would suggest that the critical event responsible for the precise sequential maturation of immunologic competence to different antigens at different developmental stages is not the first appearance of specific receptors on immunocytes. Alternative explanations of this phenomenon are discussed.

In vitro induction of a primary response to the dinitrophenyl determinant.

Primary antibody response against the dinitrophenyl group has been elicited in vitro after the stimulation of normal mouse spleen explants with 2,4-dinitrophenyl (DNP)-hemocyanin or alpha-DNP-poly-L-lysine (PLL). Antibodies were detected in the culture medium by the inactivation of DNP-T4 phage. The specificity of the reaction was manifested by the lack of the capacity of the medium to inactivate the unmodified bacteriophage and by the inhibition of the inactivation of DNP-T4 with DNP-lysine.

Ectopic pregnancy early diagnosis markers.

Ectopic pregnancy (EP) is a high-risk medical condition with an incidence of 1.9% in reported pregnancies, and has proven to be the most common cause of pregnancy-related deaths in the first trimester. The clinical symptoms can mimic non-EP conditions, thus creating a challenge for developing diagnostic criteria and new diagnostic tools. Early diagnosis of ectopic pregnancy is essential in order to minimize the morbidity and to assess the need for urgent surgical intervention. Currently, ultrasound and serum biomarkers are used by clinicians for early detection and diagnosis. This review summarizes and comments on the available literature on the various markers including their utility and their statistical parameters.

Women in refuge: Syrian women voicing health sequelae due to war traumatic experiences and displacement challenges.

OBJECTIVE: The Syrian war created a mass exodus of people to neighboring countries. Jordan hosts approximately 1.4 million Syrians who sought refuge and protection. This research represents an effort to understand the subjective narratives of Syrian refugee women's war traumatic experiences and displacement challenges while living in Jordan and the consequences on their physical and mental health. METHODS: Data gathered between March and June 2014 included 24 in-depth interviews with Syrian refugee women who sought services from humanitarian organizations in Jordan. Interviews were conducted in Arabic and were audio recorded. A team of four researchers translated and transcribed the interviews. Group narrative methodology was utilized to analyze the interviews. RESULTS: The study suggests that Syrian refugee women experienced diverse war atrocities including shelling, loss of property, separation from family members, and threats to their lives and their beloved ones, among a few. In Jordan, they reported on multiple displacement challenges, which are perceived as a continuous traumatic experience, as well as somatization. Narratives of women also included sequelae to their physical and mental health due to such stressors. Barriers to obtaining physical and mental health services are discussed, including inadequate medical treatment, lack of mental health services, and stigma on mental health, which might be associated to somatization of mental illnesses. CONCLUSION: It is crucial that humanitarian organizations and host countries like Jordan bear the responsibility to enhancing accessibility to comprehensive trauma-focused physical and mental health services for Syrian refugees in a culturally and gender sensitive manner.

Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study.

OBJECTIVES: The aim was to compare the burden of environmental shedding of toxigenic Clostridioides difficile among asymptomatic carriers, C. difficile-infected (CDI) patients and non-carriers in an inpatient non-epidemic setting. METHODS: C. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatic patients. Active CDI was defined as a positive two-step enzyme immunoassay/polymerase chain reaction (EIA/PCR) test in patients with more than three unformed stools/24 hr. C. difficile environmental contamination was assessed by obtaining specimens from ten sites in the patients' rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination. RESULTS: One hundred and seventeen rooms were screened: 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which three (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of non-carriers odd ratio 12.23 and 11.16 (95% confidence interval 1.5-99.96 p 0.0195, and 1.19-104.49 p 0.035), respectively. DISCUSSION: Here we show that the rooms of C. difficile carriers are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.

RNA-Regulated TRA-1 nuclear export controls sexual fate.

TRA-1, a member of the GLI family of transcription factors, is required for C. elegans female development. We find that TRA-1 has a sex-specific distribution consistent with its role in female development: nuclear TRA-1 is higher in hermaphrodite intestines and in specific germline regions than in males. TRA-1 patterns rely on nuclear export since treatment with leptomycin B, a CRM1-dependent export inhibitor, increases nuclearTRA-1 in males. TRA-1 export requires TRA-1 binding to the tra-2 3' untranslated region (3' UTR), as disruption of binding increases nuclear TRA-1 and female development. Our data are consistent with coexport of a TRA-1/tra-2 mRNA complex reducing TRA-1 nuclear activity, and identify an interesting RNA-based mechanism for controlling transcriptional activity and cell fate determination.

Galactose conversion to D-xylulose: an alternate route of galactose metabolism.

Galactose dehydrogenase, a soluble enzyme of the mammalian liver, catalyzes the conversion of galactose to galactonic acid. This reaction, together with the subsequent formation of 3-ketogalactonic acid which can be decarboxylated to yield d-xylulose, is a newly discovered pathway for the metabolism of galactosee. This pathway may account for the oxidation of galactose observed in pathients with galactosemia.

Electrophoretic heterogeneity of mammalian galactose dehydrogenase.

Electrophoretically distinct forms of galactose dehydrogenase were demonstrated in various tissues of the rat. Phylogenetic comparisons revealed considerable variation with species in mammalian liver zymograms; virtually no activity was demonstrable in fish, pigeon, and frog liver. Ontogenetic studies of the rat revealed sequential appearance of liver isoenzymes.

Flow control among microvessels coordinated by intercellular conduction.

Optimal distribution of blood flow requires coordination of vasodilation among resistance vessels. During hyperemia, blood vessels dilate upstream from the initiating stimulus. Spreading vasodilation independent of flow changes has not been previously demonstrated. In the present study, iontophoresis of acetylcholine adjacent to single hamster cheek pouch arterioles in situ (diameter, 20 to 37 micrometers) induced a rapid bidirectional dilation that was not attenuated when blood flow was eliminated with vascular occlusion. This finding indicates that a vasodilatory stimulus is conducted along the arteriole and demonstrates the existence of a mechanism of intercellular communication that is capable of coordinating diameter changes among resistance vessels.

Lysine transport in human kidney: evidence for two systems.

Experiments with slices of human kidney cortex from two control subjects demonstrated two distinct transport systems for lysine (alpha and beta) which differ greatly in affinity and capacity. Both systems were found in kidney from two patients with cystinuria. Studies with rat kidney confirmed these findings. These experiments defined only a single transport system for cystine in kidney from both control and cystinuric subjects.

Transport interaction of cystine and dibasic amino acids in renal brush border vesicles.

The uptake of cystine by vesicles prepared from rat kidney brush borders occurs by two distinct transport systems. The higher affinity system is inhibited by the dibasic amino acids lysine, arginine, and ornithine. The lower affinity system, unaffected by dibasic amino acids, appears to correspond to that observed by studying uptake of cystine by kidney slices.

Regulation of amino acid transport in kidney cortex of newborn rats.

After incubation at 37 degrees C the subsequent uptake of alpha-aminoisobutyric acid, cycloleucine, glycine, and L-proline by newborn (as compared to adult) rat kidney cortex slices is enhanced. The effect is abolished by the presence of cycloheximide, actinomycin D, and high concentrations of the above-mentioned amino acids in the medium during the 37 degrees C incubation prior to measurement of uptake. The data suggest that there is an adaptive control mechanism which is expressed on incubation at 37 degrees C and which can regulate amino acid transport in newborn rat kidney cortex.

Galactose toxicity in the chick: hyperosmolality.

Galactose-fed chicks have been found to develop severe hyperosmolar dehydration. Although biochemical abnormalities have been observed in the brain of the galactose-toxic chick, the observed physiologic alteration of serum osmolality could be the major factor responsible for the galactose toxicity syndrome in the chick.

Thymus-derived lymphocytes: humoral and cellular reactions distinguished by hydrocortisone.

Lymphocytes derived from the thymus (T cells) take part in the induction of humoral antibody and also effect cell-mediated graft-versus-host reactions. Preliminary treatment of mice with hydrocortisone caused an inhibition of T-cell function in humoral immunity, while enhancing the graft-versus-host reactivity of the same population of spleen cells. This suggests that different types of T cells participate in cellular and humoral immune reactions.

Sugar transport: effect of temperature on concentrative uptake of alpha-methylglucoside by kidney cortex slices.

The ability of renal cortical slices to accumulate a monosaccharide is enhanced at temperatures below 37 degrees C. Increase in concentration gradients occurs despite a decrease in total sugar flux. The apparent explanation for this paradox is a proportionally greater inhibition of efflux.