Delayed diagnosis of Townes‑Brocks syndrome with multicystic kidneys and renal failure caused by a novel SALL1 nonsense mutation: A case report

Townes‑Brocks syndrome (TBS) is a rare autosomal dominant congenital anomaly syndrome characterized by the triad of anorectal, hand and external ear malformations. Kidney involvement is less common and may progress to end‑stage renal failure (ESRF) early in life. The present study reports the case of a male patient presenting with multiple bilateral cortical kidney cysts at the age of 4 years, at which time the kidneys were of normal size and function. A clinical diagnosis of autosomal recessive polycystic kidney disease was made initially as the patient's parents are clinically healthy. However, the consideration of extra‑renal involvements (imperforate anus at birth, preaxial polydactyly and dysplastic right ear) following the progression of the patient to ESRF at the age of 16 years, led to the diagnosis of TBS. This prompted sequencing of the SALL1 gene, which identified a novel heterozygous nonsense mutation in the mutational ‘hotspot’ of exon 2 (c.874C>T, p.Q292X), and this mutation was not detected in healthy controls. The current case highlights that TBS may present with normal sized, cystic kidneys in childhood, while recognition of extra‑renal features of cystic kidney diseases, such as TBS, and genetic testing may facilitate the correct diagnosis and transmission mode. Reaching a correct diagnosis of as TBS is important since this condition has a 50% rate of transmission to offspring and can progress to ESRF early in life

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Neonatal jaundice and stool production in breast- or formula-fed term infants

It has remained unclear whether the amount of fecal fat excreted in the stool and stool production influences the severity of neonatal jaundice. We determined the relationship between stool production, fecal fat excretion and jaundice in healthy breast-fed (BF) or formula-fed (FF) (near-)term neonates. From postnatal day 1–4, we quantitatively collected stools from 27 FF and 33 BF infants in daily fractions. Stool production and fecal fat contents were related to unconjugated bilirubin (UCB) levels, as determined by transcutaneous bilirubinometry (TcB). Bilirubin concentrations and stool production did not differ between FF and BF neonates during the study period. Neonatal bilirubin levels were not inversely correlated with stool production. FF and BF infants had similar fecal fat excretion rates. The stool production of FF infants was profoundly lower in the present study than in a 1985 study by De Carvalho et al. [J Pediatr (1985) 107:786–790]. We conclude that increased jaundice during the first postnatal days in healthy term neonates can no longer be attributed to breast-feeding and speculate that improved absorbability of formulas since 1985 has contributed to similar fat excretion and stool production in FF and BF neonates in 2007

Diagnostic thinking and information used in clinical decision-making: a qualitative study of expert and student dental clinicians

<p>Abstract</p> <p>Background</p> <p>It is uncertain whether the range and frequency of Diagnostic Thinking Processes (DTP) and pieces of information (concepts) involved in dental restorative treatment planning are different between students and expert clinicians.</p> <p>Methods</p> <p>We video-recorded dental visits with one standardized patient. Clinicians were subsequently interviewed and their cognitive strategies explored using guide questions; interviews were also recorded. Both visit and interview were content-analyzed, following the Gale and Marsden model for clinical decision-making. Limited tests used to contrast data were t, χ², and Fisher's. Scott's π was used to determine inter-coder reliability.</p> <p>Results</p> <p>Fifteen dentists and 17 senior dental students participated in visits lasting 32.0 minutes (± 12.9) among experts, and 29.9 ± 7.1 among students; contact time with patient was 26.4 ± 13.9 minutes (experts), and 22.2 ± 7.5 (students). The time elapsed between the first and the last instances of the clinician looking in the mouth was similar between experts and students. Ninety eight types of pieces of information were used in combinations with 12 DTPs. The main differences found in DTP utilization had dentists conducting diagnostic interpretations of findings with sufficient certainty to be considered definitive twice as often as students. Students resorted more often to more general or clarifying enquiry in their search for information than dentists.</p> <p>Conclusions</p> <p>Differences in diagnostic strategies and concepts existed within clearly delimited types of cognitive processes; such processes were largely compatible with the analytic and (in particular) non-analytic approaches to clinical decision-making identified in the medical field. Because we were focused on a clinical presentation primarily made up of non-emergency treatment needs, use of other DTPs and concepts might occur when clinicians evaluate emergency treatment needs, complex rehabilitative cases, and/or medically compromised patients.</p

Temozolomide and cisplatin in relapsed/refractory acute leukemia

Cisplatin depletes MGMT and increases the sensitivity of leukemia cells to temozolomide. We performed a phase I study of cisplatin and temozolomide in patients with relapsed and refractory acute leukemia. Fifteen patients had AML, 3 had ALL, and 2 had biphenotypic leukemia. The median number of prior chemotherapy regimens was 3 (1–5). Treatment was well tolerated up to the maximal doses of temozolomide 200 mg/m2/d times 7 days and cisplatin 100 mg/m2 on day 1. There was one complete remission in this heavily pretreated patient population. Five of 20 (25%) patients demonstrated a significant reduction in bone marrow blasts

Envelope 2 protein phosphorylation sites S75 & 277 of hepatitis C virus genotype 1a and interferon resistance: A sequence alignment approach

<p>Abstract</p> <p>Background</p> <p>Hepatitis C is a major health problem affecting more than 200 million individuals in world including Pakistan. Current treatment regimen consisting of interferon alpha and ribavirin does not always succeed to eliminate virus completely from the patient's body.</p> <p>Results</p> <p>Interferon induced antiviral protein kinase R (PKR) has a role in the hepatitis C virus (HCV) treatment as dsRNA activated PKR has the capacity to phosphorylate the serine and threonine of E2 protein and dimerization viral RNA. E2 gene of hepatitis C virus (HCV) genotype 1 has an active role in IFN resistance. E2 protein inhibits and terminates the kinase activity of PKR by blocking it in protein synthesis and cell growth. This brings forward a possible relation of E2 and PKR through a mechanism via which HCV evades the antiviral effect of IFN.</p> <p>Conclusion</p> <p>A hybrid in-silico and wet laboratory approach of motif prediction, evolutionary and structural anlysis has pointed out serine 75 and 277 of the HCV E2 gene as a promising candidate for the serine phosphorylation. It is proposed that serine phosphorylation of HCV E2 gene has a significant role in interferon resistance.</p

Mapping medical careers: Questionnaire assessment of career preferences in medical school applicants and final-year students

BACKGROUND: The medical specialities chosen by doctors for their careers play an important part in the workforce planning of health-care services. However, there is little theoretical understanding of how different medical specialities are perceived or how choices are made, despite there being much work in general on this topic in occupational psychology, which is influenced by Holland's RIASEC (Realistic-Investigative-Artistic-Social-Enterprising-Conventional) typology of careers, and Gottfredson's model of circumscription and compromise. In this study, we use three large-scale cohorts of medical students to produce maps of medical careers. METHODS: Information on between 24 and 28 specialities was collected in three UK cohorts of medical students (1981, 1986 and 1991 entry), in applicants (1981 and 1986 cohorts, N = 1135 and 2032) or entrants (1991 cohort, N = 2973) and in final-year students (N = 330, 376, and 1437). Mapping used Individual Differences Scaling (INDSCAL) on sub-groups broken down by age and sex. The method was validated in a population sample using a full range of careers, and demonstrating that the RIASEC structure could be extracted. RESULTS: Medical specialities in each cohort, at application and in the final-year, were well represented by a two-dimensional space. The representations showed a close similarity to Holland's RIASEC typology, with the main orthogonal dimensions appearing similar to Prediger's derived orthogonal dimensions of 'Things-People' and 'Data-Ideas'. CONCLUSIONS: There are close parallels between Holland's general typology of careers, and the structure we have found in medical careers. Medical specialities typical of Holland's six RIASEC categories are Surgery (Realistic), Hospital Medicine (Investigative), Psychiatry (Artistic), Public Health (Social), Administrative Medicine (Enterprising), and Laboratory Medicine (Conventional). The homology between medical careers and RIASEC may mean that the map can be used as the basis for understanding career choice, and for providing career counselling

Childhood emotional problems and self-perceptions predict weight gain in a longitudinal regression model

<p>Abstract</p> <p>Background</p> <p>Obesity and weight gain are correlated with psychological ill health. We predicted that childhood emotional problems and self-perceptions predict weight gain into adulthood.</p> <p>Methods</p> <p>Data on around 6,500 individuals was taken from the 1970 Birth Cohort Study. This sample was a representative sample of individuals born in the UK in one week in 1970. Body mass index was measured by a trained nurse at the age of 10 years, and self-reported at age 30 years. Childhood emotional problems were indexed using the Rutter B scale and self-report. Self-esteem was measured using the LAWSEQ questionnaire, whilst the CARALOC scale was used to measure locus of control.</p> <p>Results</p> <p>Controlling for childhood body mass index, parental body mass index, and social class, childhood emotional problems as measured by the Rutter scale predicted weight gain in women only (least squares regression <it>N </it>= 3,359; coefficient 0.004; <it>P </it>= 0.032). Using the same methods, childhood self-esteem predicted weight gain in both men and women (<it>N </it>= 6,526; coefficient 0.023; <it>P </it>< 0.001), although the effect was stronger in women. An external locus of control predicted weight gain in both men and women (<it>N </it>= 6,522; coefficient 0.022; <it>P </it>< 0.001).</p> <p>Conclusion</p> <p>Emotional problems, low self-esteem and an external locus of control in childhood predict weight gain into adulthood. This has important clinical implications as it highlights a direction for early intervention strategies that may contribute to efforts to combat the current obesity epidemic.</p