Routine colonoscopy with a surprise in the cecum: It's a giant appendicolith! A Case report and review of the literature.

Giant appendicoliths (defined as appendiceal stones larger than 2 cm in size) are rare findings, with less than 20 well-documented reported cases. Appendicoliths, in general, are linked to an increased risk of appendicitis and associated complications. However, little information is available on the clinical impact of giant appendicoliths. We present a case of a giant appendicolith accidentally discovered during screening colonoscopy. With more than 4 cm, this appendicolith is one of the largest of the few reported so far. In contrast to all other cases of giant appendicoliths, the patient did not exhibit any symptoms. Additionally, we provide an overview of giant appendicolith cases, discussing their clinical features, diagnosis, and treatment.

Sonographically Detected Hepatic Portal Venous Gas - Prevalence, Causes, and Clinical Implications.

PURPOSE: Hepatic portal venous gas (HPVG) is a rare clinical finding, often caused by a severe underlying disease. In the literature as well as in clinical practice, HPVG is considered "signum malum" with a poor prognosis and bowel ischemia as the most common cause. Most studies are based on the results of computed tomography (CT) examinations. The aim of this retrospective study is to report on the prevalence, causes, and clinical course of HPVG in a monocentric cohort of abdominal ultrasound (US) investigations. MATERIALS AND METHODS: The US database of an academic teaching hospital was searched with specific keywords (timespan 01/2000 to 12/2020). Reports, pictures, and clinical data of all cases with HPVG were re-evaluated. RESULTS: Out of 134 804 US examinations, 8 HPVG cases were identified. There was a wide variety of underlying diseases, with mesenteric ischemia being seen in only 2 cases. 5 patients were discharged in stable condition, with 4 of them having undergone surgical treatment. 2 patients who had rejected further measures died, and one was lost to follow-up. DISCUSSION: HPVG is a rare phenomenon in clinical US. However, ultrasonographic prevalence is comparable to the prevalence in CT studies. Underlying diseases are mostly severe, and in nearly all cases an underlying cause can be found by thorough investigation. In some cases, US may even be superior to CT scans for the detection of HPVG. Despite its rarity, every sonographer should know the typical sonographic presentation of HPVG, and appropriate images should be included in US teaching modules.

To Be in Harmony: Chinese American Adolescents' and Parents' Bicultural Integration During the COVID-19 Pandemic.

Experiences of racial discrimination have been found to be associated with internalizing problems among ethnic-racial minority youth. However, mediating and moderating processes that might explain this association is less well understood. Thus, the present study aimed to examine whether Chinese American adolescents' bicultural identity integration harmony (BII-Harmony) mediated the association between their experiences of racial discrimination and internalizing behaviors. Furthermore, we examined the moderating role of their parents' BII-Harmony in this mediation model. Chinese American adolescents (Mage = 13.9 years; SD = 2.3; 48% female) reported their experiences of racial discrimination and BII-Harmony, and their parents (Mage = 46.2 years; SD = 5.2; 81% mothers) reported their BII-Harmony and their children's internalizing difficulties. Chinese American adolescents' racial discrimination experiences were negatively associated with BII-Harmony, and in turn, more internalizing problems, but only when their parents also reported low and mean levels of BII-Harmony.

[Lung Ultrasound on Admission to a Covid Decision Unit - Helpful in Differential Diagnosis or a Waste of Time?] / Thoraxsonografie bei Aufnahme auf einer COVID-Verdachtsstation ­ differenzialdiagnostisch hilfreich oder Zeitverschwendung?

BACKGROUND: In patients with Covid-19, typical and often severe lung lesions have been reported. In addition to the use of chest CT, the diagnostic benefit of lung ultrasound has been advocated.This trial investigates if in patients presenting with symptoms compatible with Covid-19, lung ultrasound is of use in the early differential diagnosis. METHODS: This study includes 46 patients of the first wave of the Covid-19 pandemic (23 with confirmed infection, 23 controls with later on excluded infection), who were initially admitted to the Covid Decision Unit of an academic teaching hospital under the clinical suspicion of SARS-CoV-2 infection. All patients were examined by pulmonary ultrasound shortly after admission. The final diagnosis of infection was made or ruled out by means of - sometimes repeated - PCR of nasal/pharyngeal swabs.Findings of SARS-CoV-2 patients and controls were compared and analyzed for significant differences in chest sonographic parameters. RESULTS: There were significant differences in the lung ultrasound findings of both groups. In the Covid group there were significantly fewer A-lines, more pathological B-lines (increased or confluent) and more consolidations. Pleural effusions were significantly more frequent in the control group. The calculated lung ultrasound score (LUS) was higher in the Covid group than in the control group. However, a reliable differentiation between the two groups was not possible due to the wide range and overlap.  CONCLUSION: In a clinical setting, lung ultrasound reveals more frequent and different lesions in SARS-CoV-2 infected patients than in patients in whom the initial clinical suspicion was not confirmed. However, due to the overlap of findings between the two groups, lung ultrasound was not suitable to differentiate with sufficient certainty between SARS-CoV-2 infected and non-infected patients.

Straight Vessel Pattern and Rapid Filling Time: Characteristic Findings on Contrast-Enhanced Sonography of Testicular Lymphoma.

Six patients with 7 lesions that were histologically confirmed as primary testicular lymphoma were preoperatively investigated with a standardized sonographic protocol including contrast-enhanced sonography. Duplex and contrast-enhanced sonography showed marked hypervascularization in all 7 lesions. On contrast-enhanced sonography, the filling time of lymphomatous lesions was significantly shorter than the filling time of a size-matched sample of 10 patients with seminomas (P < .0001). The sonographic hallmarks of testicular lymphoma in our case series were as follows: (1) sharply demarcated homogeneous hypoechoic testicular lesions with marked hypervascularization; (2) a rapid (<7 seconds) filling time of contrast bubbles; and (3) a straight and parallel course of intralesional vessels on contrast-enhanced sonography.

Lynch syndrome associated with two MLH1 promoter variants and allelic imbalance of MLH1 expression.

Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) within the MLH1 5'untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expression and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A>G and c.-7C>T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5'UTR in the pathogenesis of Lynch syndrome.

Increased titers of neutralizing antibodies after immunization with both envelope proteins of the porcine endogenous retroviruses (PERVs).

Despite enormous difficulties to induce antibodies neutralizing HIV-1, especially broadly neutralizing antibodies directed against the conserved membrane proximal external region (MPER) of the transmembrane envelope protein, such antibodies can be easily induced in the case of gammaretroviruses, among them the porcine endogenous retroviruses (PERVs). In addition to neutralizing antibodies directed against the transmembrane envelope protein p15E, neutralizing antibodies were also induced by immunization with the surface envelope protein gp70. PERVs represent a special risk for xenotransplantation using pig tissues or organs since they are integrated in the genome of all pigs and infect human cells and a vaccine may protect from transmission to the recipient. To investigate the effect of simultaneous immunization with both proteins in detail, a study was performed in hamsters. Gp70 and p15E of PERV were produced in E. coli, purified and used for immunization. All animals developed binding antibodies against the antigens used for immunization. Sera from animals immunized with p15E recognized epitopes in the MPER and the fusion peptide proximal region (FPPR) of p15E. One MPER epitope showed a sequence homology to an epitope in the MPER of gp41 of HIV-1 recognized by broadly neutralizing antibodies found in HIV infected individuals. Neutralizing antibodies were detected in all sera. Most importantly, sera from animals immunized with gp70 had a higher neutralizing activity when compared with the sera from animals immunized with p15E and sera from animals immunized with gp70 together with p15E had a higher neutralizing activity compared with sera from animals immunized with each antigen alone. These immunization studies are important for the development of vaccines against other retroviruses including the human immunodeficiency virus HIV-1.

Biomimic Vein-Like Transparent Conducting Electrodes with Low Sheet Resistance and Metal Consumption.

In this contribution, inspired by the excellent resource management and material transport function of leaf veins, the electrical transport function of metallized leaf veins is mimicked from the material transport function of the vein networks. By electroless copper plating on real leaf vein networks with copper thickness of only several hundred nanometre up to several micrometre, certain leaf veins can be converted to transparent conductive electrodes with an ultralow sheet resistance 100 times lower than that of state-of-the-art indium tin oxide thin films, combined with a broadband optical transmission of above 80% in the UV-VIS-IR range. Additionally, the resource efficiency of the vein-like electrode is characterized by the small amount of material needed to build up the networks and the low copper consumption during metallization. In particular, the high current density transport capability of the electrode of > 6000 A cm-2 was demonstrated. These superior properties of the vein-like structures inspire the design of high-performance transparent conductive electrodes without using critical materials and may significantly reduce the Ag consumption down to < 10% of the current level for mass production of solar cells and will contribute greatly to the electrode for high power density concentrator solar cells, high power density Li-ion batteries, and supercapacitors.

Structure of Ni(OH)2 intermediates determines the efficiency of NiO-based photocathodes - a case study using novel mesoporous NiO nanostars.

We report the wet chemical synthesis of mesoporous NiO nanostars (NS) as photocathode material for dye-sensitized solar cells (DSSCs). The growth mechanism of NiO NS as a new morphology of NiO is assessed by TEM and spectroscopic investigations. The NiO NS are obtained upon annealing of preformed ß-Ni(OH)2 into pristine NiO with low defect concentrations and favorable electronic configuration for dye sensitization. The NiO NS consist of fibers self-assembled from nanoparticles yielding a specific surface area of 44.9 m2 g-1. They possess a band gap of 3.83 eV and can be sensitized by molecular photosensitizers bearing a range of anchoring groups, e.g. carboxylic acid, phosphonic acid, and pyridine. The performance of NiO NS-based photocathodes in photoelectrochemical application is compared to that of other NiO morphologies, i.e. nanoparticles and nanoflakes, under identical conditions. Sensitization of NiO NS with the benchmark organic dye P1 leads to p-DSSCs with a high photocurrent up to 3.91 mA cm-2 whilst the photoelectrochemical activity of the NiO NS photocathode in aqueous medium in the presence of an irreversible electron acceptor is reflected by generation of a photocurrent up to 23 µA cm-2.

Real-Time Elastography and Contrast-Enhanced Ultrasonography in the Evaluation of Testicular Masses: A Comparative Prospective Study.

This study investigates the usefulness of contrast-enhanced ultrasound (CEUS) and real-time elastography (RTE) for the characterization of testicular masses by comparing pre-operative ultrasound findings with post-operative histology. Sixty-seven patients with 68 sonographically detected testicular masses underwent B-mode, color-coded Doppler sonography (CCDS), CEUS and RTE according to defined criteria. For RTE, elasticity score (ES), difference of elasticity score (D-ES), strain ratio (SR) and size quotient (Qsize) were evaluated. Histopathologically, 54/68 testicular lesions were neoplastic (47 malignant, 7 benign). Descriptive statistics revealed the following results (neoplastic vs. non-neoplastic) for sensitivity, specificity, positive predictive value, negative predictive value and accuracy, respectively: B-mode, 100%, 43%, 87%, 100%, 88%; CCDS 81%, 86%, 96%, 55%, 82%; CEUS 93%, 85%, 96%, 73%, 91%; ES 98%, 25%, 85%, 75%, 85%; D-ES 98%, 50%, 90%, 83%, 89%; SR 90%, 45%, 86%, 56%, 81%; and Qsize 57%, 83%, 94%, 28%, 61%. B-mode with CCDS remains the standard for assessing testicular masses. In characterization of testicular lesions, CEUS clearly outperformed all other modalities. Our study does not support the routine use of RTE in testicular ultrasonography because of its low specificity.

Early experience with contrast-enhanced ultrasound in the diagnosis of testicular masses: a feasibility study.

OBJECTIVE: To evaluate the feasibility of contrast-enhanced ultrasound (CEUS) in the diagnosis of testicular masses. METHOD: A total of 51 consecutive patients with testicular masses detected by clinical examination and gray-scale ultrasound were examined with CEUS (2.4 mL of intravenous Sonovue [Bracco]) before surgery. Characteristics of contrast enhancement were correlated with intraoperative and histologic findings. RESULTS: In 50/51 patients, bubbles of the contrast media were clearly visualized in the testicles 21 ± 5.5 seconds after injection. Of the patients, 43 had a neoplastic lesion, histologically (29 seminoma, 9 nonseminomatous testicular tumor, 4 Leydig cell tumor, and 1 non-Hodgkin lymphoma). In 39 of 51 patients (76.5%), testicular masses showed a clear early hyperenhancement compared with the surrounding tissue. Of these 39 masses, 38 proved to be neoplastic; 1 patient had focal suppurative epididymo-orchitis. Hyperenhancement of a testicular lesion had a positive predictive value of 97.4% (95% CI = 84.9-99.9%) for neoplasia. Hyperenhancement was not found in 7 of 8 lesions proved to be nonneoplastic (1 epidermoid cyst, 3 necrosis/atrophy, 1 incarcerated inguinal hernia, 1 hematoma, and 1 tubular ectasia of the rete testis). CONCLUSIONS: CEUS allows visualization of testicular microvascularization and may thus aid in the preoperative assessment of testicular lesions with hypervascularization as an important feature in the diagnosis of malignancy. It may be particularly valuable in the assessment of small intratesticular masses where color-coded ultrasound comes to its limits.

Putting the positive in health psychology: a content analysis of three journals.

This content analysis investigated the inclusion of positive psychological constructs in research published in three leading health psychology journals. A list of positive constructs relevant to health psychology was compiled and their inclusion in these journals was examined. It was found that although there has been a sharp increase in recent years, only 3 percent of all articles published (114 of 3789) included the study of overtly positive constructs. The constructs that have been most and least studied in health psychology were identified and are discussed. This analysis provides insight into the foundations of positive health psychology and identifies future directions.

Repeated siRNA application is a precondition for successful mRNA gammaENaC knockdown in the murine airways.

The volume of the airway surface liquid is regulated by Na(+) absorption and Cl(-) secretion by the respiratory epithelium. In cystic fibrosis, Na(+) hyperabsorption caused by the absence of functional CFTR protein leads to an altered airway surface liquid composition and finally to a deteriorated mucociliary clearance. It has been suggested that down regulation or inhibition of the amiloride-sensitive epithelial Na(+) channel (ENaC) could restore the disrupted airway hydration. Therefore, targeting ENaC by RNA interference could be of therapeutic relevance. In this context, we investigated whether RNAi could lead to a reduction in gammaENaC expression in epithelia in vitro and in vivo in mice. Transfection of cells with specific siRNA sequences for gammaENaC subunit reduced expression to approximately 10% relative to control. For in vivo experiments, siRNA sequences specific for the gammaENaC subunit were administered to the murine nasal cavity and, 72h later the animals were killed. In the first approach, only a single application of naked siRNA was given. In the second approach, repeated siRNA applications were performed. The single application of siRNA sequences had no effect on mRNA content of the targeted gammaENaC subunit, whereas repeated siRNA application resulted in a significant reduction in gammaENaC mRNA in the respiratory tissue. We conclude that repeated siRNA application is necessary for gammaENaC knockdown in the murine airways.

Functional analysis of PKHD1 splicing in autosomal recessive polycystic kidney disease.

Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the PKHD1 (polycystic kidney and hepatic disease 1) gene on chromosome 6p12. The longest continuous open reading frame comprises 66 exons encoding a novel 4,074 aa multidomain integral membrane protein (polyductin/fibrocystin) of unknown function. Various alternatively spliced transcripts may additionally result in different isoproteins. Overall, the large size of PKHD1, its complex pattern of splicing, multiple allelism and lack of knowledge of the encoded protein's/proteins' functions pose significant challenges to DNA-based diagnostic testing. Nucleotide substitutions, particularly if residing in regulatory elements or introns outside the splice consensus sites, are often difficult to assess without further functional analyses and cannot be unambiguously classified as disease-associated. Investigations on the transcript level, however, are hampered as PKHD1 is not widely expressed in blood lymphocytes. We thus determined the functional significance of the novel splice site mutation c.53-3C>A in intron 2 by RNA analyses by minigene-construction. The mutant allele was shown to cause skipping of exon 3. Thus, given the minigene results together with 400 control chromosomes negative for this change, segregation of the mutation with the phenotype, and a significant lowering of the strength of the splice site by bioinformatics, the mutant allele is most likely pathogenic. To the best of our knowledge, this is the first study that defines the consequences of a PKHD1 splice mutation and underlines the relevance of functional analyses in determining the pathogenicity of changes of unknown significance.

Identification of novel cystinuria mutations in pediatric patients.

OBJECTIVE: Cystinuria is a common inherited disorder of renal reabsorption of cystine and the dibasic amino acids. So far, mutations in two genes (SLC3A1 and SLC7A9) have been identified in cystinuria patients. Molecular searches for cystinuria mutations show that their distribution depends on the ethnic origin of the patients, but have not allowed the detection of 100% of variants. Pediatric patients representing a severe form of the disease appear to carry other mutations than those patients referred from urological centers. We analysed patients with an age of manifestation less than 15 years for mutations in the two cystinuria genes. PATIENTS AND METHODS: We screened 17 patients for mutations in SLC3A1 and SLC7A9, 15 of whom were younger than 16 years at first stone formation. The search for mutations used PCR-based standard techniques, and was focused on point mutations and larger deletions and duplications in both genes. RESULTS: Apart from detection of mutations in approximately 70% of patients but identification of only 53% of alleles, we detected three novel mutations as well as three new polymorphisms. CONCLUSION: The detection rate in young cystinuria patients is lower than that in older patients, and there is a different pattern of variants. There is evidence for other (probably genetic) factors being involved in the pathophysiology of cystinuria.

Functional analysis of a new splice site mutation, c.605-3C>A, in the cystinuria gene SLC7A9 leading to exon skipping.

Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. While mutations in the SLC3A1 gene cause type I cystinuria, patients with non-type I cystinuria carry mutations in the SLC7A9 gene. Up to now, more than 80 mutations in SLC3A1 and 50 in SLC7A9 have been reported in the literature. While deletions, duplications, and truncating mutations can often unambiguously classified to be pathogenic, the functional relevance of base pair substitutions is often difficult to predict. To determine the functional relevance of a new splice site mutation in intron 5 of SLC7A9, c.605-3C>A, we transfected COS7 cells with expression constructs containing the wild-type and mutant allele, respectively. cDNAs derived from the resulting SLC7A9 mRNAs were sequenced. By this approach we could demonstrate that the mutant allele c.605-3A causes exon skipping and therefore represents a splice site mutation. To the best of our knowledge, this is the first splice site mutation in a cystinuria gene with a proven functional consequence.

The population-specific distribution and frequencies of genomic variants in the SLC3A1 and SLC7A9 genes and their application in molecular genetic testing of cystinuria.

Cystinuria is a common inherited aminoaciduria resulting in nephrolithiasis. Mutations in two genes, SLC3A1 and SLC7A9, have been identified in cystinuric patients. Considering the population-specific distribution of genetic variants in the SLC3A1 gene, we focused our study on mutations in SLC3A1 and SLC7A9 described more than once in the literature. We evaluated the usefulness of this restricted analysis as a diagnostic approach. Furthermore, the data obtained were used to estimate the frequency of heterozygote carriers of SLC3A1 mutations in the general European population. A total of 22 unclassified cystinuric patients were screened for genetic variants in four exons of both SLC3A1 and SLC7A9 in which the most common mutations have been identified. For screening, we used single strand conformation polymorphism analysis (SSCP), restriction assays, real-time PCR and direct sequencing. In total, we identified mutations in 17 of our 22 patients, including a new mutation (R365Q) as well as a novel polymorphism (c.1035G/A) within the SLC3A1 gene. An ethnic influence on the distribution of mutations was confirmed: T216M in SLC3A1 is the major mutation in south-eastern Europe, whereas M467T in SLC3A1 is mainly found in western Europe. A complex duplication in SLC3A1 is restricted to German patients. Generally, we could show that a stepwise analysis directed to the most common mutations in the two cystinuria genes is sufficient to detect variants in more than 75% of patients of European origin. The test consists of nine different PCR-based approaches and therefore represents a low-cost, reliable and timesaving diagnostic tool.

Cystinuria in children: distribution and frequencies of mutations in the SLC3A1 and SLC7A9 genes.

BACKGROUND: Cystinuria is a common inherited disorder of defective renal reabsorption of cystine, ornithine, lysine and arginine leading to nephrolithiasis. Two responsible genes have been identified so far: Mutations in the SLC3A1 gene encoding the heavy chain rbAT of the renal cystine transport system rbAT/b(0,+)AT cause cystinuria type I, while variants in SLC7A9, the gene of its light chain b(0,+)AT, have been demonstrated in non-type I cystinuria. In this study, we searched for mutations in both genes in a cohort of children with cystinuria. METHODS: Twenty-one cystinuric children from 16 families were analyzed by mutational analysis of the genes SLC3A1 and the SLC7A9. The patients were classified by the urinary amino acid excretion profile of their parents. Additionally, 10 unclassified patients were screened for genomic variants. The screening techniques included single strand conformation polymorphism analysis, restriction assays and direct sequencing. RESULTS: Two novel mutations were identified in SLC3A1 and three in SLC7A9; three were missense mutations and two frameshift mutations. In the pediatric patients, mutations were found in 54% of type I (SLC3A1) and in 25% of non-type I (SLC7A9) chromosomes. For this group of patients a total detection rate of 46.6% for mutations in both genes was delineated. In the cohort of unclassified 10 patients, 70% of mutations were determined. M467T and G105R were the preponderant mutations in SLC3A1 and SLC7A9, respectively; T216M was the major mutation in Turkey and Greece. CONCLUSIONS: The detection rate for mutations in SLC3A1 and SLC7A9 in children was 54% in the SLC3A1 gene for type I chromosomes and 25% in the SLC7A9 gene for non-type I chromosomes. It was lower than that in 10 further patients with an unclassified cystinuria, although the clinical characterization in the first group was more stringent; additionally, different spectrums of mutations were observed. The lack of detectable mutations in many patients indicates the possibility of other yet unidentified genes involved in cystinuria. We could not correlate the severity of the disease to the type of cystinuria in the pediatric patients.

Significant contribution of genomic rearrangements in SLC3A1 and SLC7A9 to the etiology of cystinuria.

BACKGROUND: Cystinuria is an inherited disorder of defective renal reabsorption of cystine and the dibasic amino acids. Recently, SLC3A1 and SLC7A9 have been identified as responsible genes. While point mutations in the two genes are well known to cause cystinuria, only a few studies are aimed on the identification of gross genomic alterations. Here, we report our results of a systematic screening for deletions and duplications in SLC3A1 and SLC7A9 by quantitative real-time polymerase chain reaction (PCR). METHODS: We screened a cohort of 49 cystinurics for copy number deviations in the genes SLC3A1 and SLC7A9 by quantitative real-time PCR assays using fluorogenic 5' nuclease chemistry. The detected duplication in SLC3A1 was analyzed in detail by further real-time assays, reverse transcription (RT)-PCR and direct sequencing. RESULTS: In seven patients, we could identify a large duplication in SLC3A1 spanning from intron 4 to intron 9. This tandem duplication was accompanied by a small inversion of 25 bp and a 2 bp deletion in intron 9. As a formation mechanism, we presume that the inversion in intron 9 and several Alu sequences neighbored to the affected region provoke a chromatin structure that stimulates the duplication event. In addition to the SLC3A1 duplication, we observed deletions in SLC7A9 in three patients. CONCLUSION: The frequency of genomic rearrangements in our patient population illustrates the significant contribution of large genomic alterations to the mutation spectrum in cystinuria. As we could show, quantitative real-time PCR is a reliable and effective tool for the identification of unbalanced genomic rearrangements.