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Objective: Primary hyperparathyroidism (PHPT) affects approximately 0.86% of the population, with surgical resection as the treatment of choice. A 4D computed tomography (CT) is a highly effective tool in localizing parathyroid adenomas; however, there is currently no defined role for 4D CT when stratified against ultrasonography (USG) and nuclear medicine Technetium Sestamibi SPECT/CT (SES) imaging., Study Design: Retrospective Study., Setting: University Hospital., Methods: All patients who underwent parathyroidectomy for PHPT between 2014 and 2019 at a single institution were reviewed. Patients who had a 4D CT were included. We compared outcomes of 4D CT as a second line imaging modality to those of USG and SES as first line modalities. An imaging algorithm was proposed based on these findings., Results: There were 84 patients identified who had a 4D CT after unsuccessful first line imaging. A 4D CT localized parathyroid adenoma to the correct quadrant in 64% of cases, and to the correct laterality in 75% of cases. Obese patients had significantly lower rates of adenoma localization with USG (33.4%), compared to non-obese patients (67.5%; P  = .006). In determining multigland disease the sensitivity of 4D CT was 86%, while the specificity was 87%., Conclusions: A 4D CT has impressive rates of accurate localization of parathyroid adenomas; however due to the radiation exposure involved, it should remain a second line imaging modality. PHPT patients should first be evaluated with USG, with 4D CT used if this is unsuccessful and patients are greater than 40 years old, have a high BMI, or are having revision surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Narcolepsy is associated with reduced quality of life and physical performance. The study aimed to explore the attitudes of people with Type 1 narcolepsy towards exercise and physical activity, their physical wellbeing, and the potential role of physiotherapy. Semi-structured interviews were conducted with 22 people with narcolepsy attending a dedicated outpatient narcolepsy clinic located in Dublin, Ireland. Transcripts were iteratively coded; a thematic analysis was undertaken, and key themes were identified. Four themes were identified: 'Barriers and Facilitators to Exercising', 'Social Concerns', 'Health Concerns' and 'Suggestions for the Role of Physiotherapy'. Future research should explore the potential role of exercise to help manage narcolepsy-related symptoms in this population., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

This work focuses on simulating the thermal history of a vertical wall consisting of a thermoplastic composite material, poly(ethylene terephthalate) glycol (PETG) with short carbon fiber reinforcement, manufactured using a Big Area Additive Manufacturing (BAAM) system. The incremental deposition process used in additive manufacturing, which corresponds to the repeated deposition of hot material onto cooler material, contributes to the presence of residual stresses and part warping. The prediction of these mechanisms is dependent on thermal history of the part, and the major motivation of this work was to improve the accuracy of finite element (FE) models used to quantify the thermal history of large-format additively manufactured parts. Thermocouples were placed throughout the part at varying heights to measure temperature as a function of time. The FE model developed found a thermal contact conductance between the printed part and the bed of 10 W/m 2 K and convection coefficient values that linearly varied from 3 to 15 W/m 2 K through the wall height when making a temperature comparison with the output from the thermocouples. It is also demonstrated that the FE model with a constant convection coefficient under-predicts model temperature at the beginning of the manufacturing process when compared against the model with a variable convection coefficient. The impact of this difference was seen in the stress values, which were larger for the model with a constant convection coefficient. Finally, a correlation equation was derived which allows the findings to be generalized to other vertical structures manufactured on the BAAM. In summary, this work offers valuable insights on material characterization, real-time thermocouple placement, and FE modeling of large-format additively manufactured parts.

Large format polymer extrusion-based additive manufacturing has been studied recently due to its capacity for high throughput, customizable bead size and geometry, and ability to manufacture large parts. Samples from three fiber-filled amorphous thermoplastic materials 3D printed using a Masterprint 3X machine from Ingersoll Machine Tools were studied, along with their neat counterparts. Characterization techniques included thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and thermo-mechanical analysis (TMA). TGA results showed that the fillers decreased the degradation temperature for most of the materials investigated, with a 30 °C decrease for polycarbonate (PC) and a 12 °C decrease for polyethylene terephthalate glycol (PETG). For all the materials used, heat capacity increases with increasing temperature. Moreover, results show that a highly conductive filler increases the heat capacity. In contrast, a material with a lower conductivity decreases the heat capacity indicated in the 15.2% and 2.54% increase for acrylonitrile butadiene styrene (ABS) and PC and a 27.68% decrease for PETG. The TMA data show that the printed bead exhibits directional properties consistent with an orthotropic material. Smaller strains and coefficient of thermal expansion (CTE) were measured along the bead direction and across the bead compared to the through bead thickness showing that fillers are predominantly oriented in the bead direction, which is consistent with the literature. CTE values through bead thickness and neat material are similar in magnitude, which corresponds to the CTE of the matrix material. The experimental results serve to characterize the effect of fiber filler on the part thermal strains in three principal directions and two-part locations during the extrusion and bead deposition of large-format polymer extrusion-based additive manufacturing technologies.

Primary hyperparathyroidism can be asymptomatic or symptomatic, as well as classic, normocalcemic, or normohormonal. It is important to rule out other causes of hypercalcemia or hyperparathyroidism. Preoperative localization with imaging is necessary for a minimally invasive approach and can be helpful even if planning 4-gland exploration. There are a variety of intraoperative techniques that can assist with localization as well as confirming success. Standard of care remains surgical resection of affected glands. However, there are less invasive management strategies that can be considered for poor surgical candidates., Competing Interests: Disclosure Nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We report the first case of extreme hypercalcemia (Ca 2+ >6.0 mmol/L) as the initial presentation of de novo metastatic breast cancer. Following treatment and stabilization of the patient, imaging revealed a large breast mass and widespread osseous metastases. Whole body bone scintigraphy demonstrated significant extra osseous uptake of radiotracer in the lungs, liver, and kidneys-a rare phenomenon secondary to profound hypercalcemia. Biopsy revealed estrogen receptor (ER) positive breast carcinoma, for which the patient was treated., (© 2020 Wiley Periodicals, Inc.)

Introduction: Preoperative carbohydrate loading is an effective method to control postoperative insulin resistance. However, data are limited concerning the effects of carbohydrate loading on preoperative hyperglycemia and possible impacts on complication rates., Methods: A prospective cohort study was performed of patients enrolled in an enhanced recovery after surgery pathway at a single institution. All patients underwent laparotomy for known or suspected gynecologic malignancies. Patients who had been diagnosed with diabetes preoperatively and those prescribed total parenteral nutrition by their providers were excluded. Data regarding preoperative carbohydrate loading with a commercial maltodextrin beverage, preoperative glucose testing, postoperative day 1 glucose, insulin administration, and complications (all complications, infectious complications, and hyperglycemia-related complications) were collected. The primary endpoint of the study was the incidence of postoperative infectious complications, defined as superficial or deep wound infection, organ/space infection, urinary tract infection, pneumonia, sepsis, or septic shock., Results: Of 415 patients, 76.9% had a preoperative glucose recorded. The mean age was 60.5±12.4 years (range 18-93). Of those with recorded glucose values, 30 patients (9.4%) had glucose ≥180 mg/dL, none of whom were actually given insulin preoperatively. Median preoperative glucose value was significantly increased after carbohydrate loading (122.0 mg/dL with carbohydrate loading vs 101.0 mg/dL without, U=3143, p=0.001); however, there was no relationship between carbohydrate loading and complications. There was a significantly increased risk of hyperglycemia-related complications with postoperative day 1 morning glucose values ≥140 mg/dL (OR 1.85, 95% CI 1.07 to 3.23; p=0.03). Otherwise, preoperative and postoperative hyperglycemia with glucose thresholds of ≥140 mg/dL or ≥180 mg/dL were not associated with increased risk of other types of complications., Discussion: Carbohydrate loading is associated with increased preoperative glucose values; however, this is not likely to be clinically significant as it does not have an impact on complication rates. Preoperative hyperglycemia is not a risk factor for postoperative complications in a carbohydrate-loaded population when known diabetic patients are excluded., Precis: While glucose increased with carbohydrate loading in non-diabetic patients, this was not associated with complications., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

We set out to investigate whether a de-novo paradigm could explain genetic causes of chronic ultra-refractory epilepsy, with onset later than the typical age for the epileptic encephalopathies. We performed exome sequencing on nine adult patients with MRI-negative epilepsy and no preceding intellectual disability. All had an onset of seizures after five years old and had chronic ultra-refractory epilepsy defined here as having failed more than six anti-epileptic drugs and currently experiencing ≥4 disabling seizures per month. Parents were sequenced to identify de-novo mutations and these were assessed for likelihood of pathogenicity based on the American College of Medical Genetics and Genomics (ACMG) criteria. We confirmed the presence of functional and predicted-damaging de-novo mutations in 3/9 patients. One of these pathogenic de-novo mutations, in DNM1L, was previously reported in a patient with severe epilepsy and chronic pharmacoresistance adding to the evidence for DNM1L as an epilepsy gene. Exome sequencing is a successful strategy for identifying de-novo mutations in paediatric epileptic encephalopathies and rare neurological disorders. Our study demonstrates the potential benefit of considering ultra-refractory epilepsy patients with later onset for genetic testing. Identifying genetic mutations underpinning severe epilepsy of unknown aetiology may provide new insight into the underlying biology and offers the potential for therapeutic intervention in the form of precision medicine in older patients., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Clinical and genetic predictors of response to antiepileptic drugs (AEDs) are largely unknown. We examined predictors of lacosamide response in a real-world clinical setting., Methods: We tested the association of clinical predictors with treatment response using regression modeling in a cohort of people with refractory epilepsy. Genetic assessment for lacosamide response was conducted via genome-wide association studies and exome studies, comprising 281 candidate genes., Results: Most patients (479/483) were treated with LCM in addition to other AEDs. Our results corroborate previous findings that patients with refractory genetic generalized epilepsy (GGE) may respond to treatment with LCM. No clear clinical predictors were identified. We then compared 73 lacosamide responders, defined as those experiencing greater than 75% seizure reduction or seizure freedom, to 495 nonresponders (<25% seizure reduction). No variants reached the genome-wide significance threshold in our case-control analysis., Significance: No genetic predictor of lacosamide response was identified. Patients with refractory GGE might benefit from treatment with lacosamide., Competing Interests: This work was funded by an Investigator‐Initiated Study award from UCB‐Pharma. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (© 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.)

Purpose: Defects in the cohesin pathway are associated with cohesinopathies, notably Cornelia de Lange syndrome (CdLS). We aimed to delineate pathogenic variants in known and candidate cohesinopathy genes from a clinical exome perspective., Methods: We retrospectively studied patients referred for clinical exome sequencing (CES, N = 10,698). Patients with causative variants in novel or recently described cohesinopathy genes were enrolled for phenotypic characterization., Results: Pathogenic or likely pathogenic single-nucleotide and insertion/deletion variants (SNVs/indels) were identified in established disease genes including NIPBL (N = 5), SMC1A (N = 14), SMC3 (N = 4), RAD21 (N = 2), and HDAC8 (N = 8). The phenotypes in this genetically defined cohort skew towards the mild end of CdLS spectrum as compared with phenotype-driven cohorts. Candidate or recently reported cohesinopathy genes were supported by de novo SNVs/indels in STAG1 (N = 3), STAG2 (N = 5), PDS5A (N = 1), and WAPL (N = 1), and one inherited SNV in PDS5A. We also identified copy-number deletions affecting STAG1 (two de novo, one of unknown inheritance) and STAG2 (one of unknown inheritance). Patients with STAG1 and STAG2 variants presented with overlapping features yet without characteristic facial features of CdLS., Conclusion: CES effectively identified disease-causing alleles at the mild end of the cohensinopathy spectrum and enabled characterization of candidate disease genes.

Background: Gastroparesis is difficult to treat and many patients do not report relief of symptoms with medical therapy alone. Several operative approaches have been described. This study shows the results of our selective surgical approach for patients with gastroparesis., Materials and Methods: This is a retrospective study of prospective data from our electronic medical record and data symptom sheet. All patients had a pre-operative gastric emptying study showing gastroparesis, an esophagogastroduodenoscopy, and either a CT or an upper GI series with small bowel follow-through. All patients had pre- and post-operative symptom sheets where seven symptoms were scored for severity and frequency on a scale of 0-4. The scores were analyzed by a professional statistician using paired sample t test., Results: 58 patients met inclusion criteria. 33 had gastric stimulator (GES), 7 pyloroplasty (PP), 16 with both gastric stimulator and pyloroplasty (GSP), and 2 sleeve gastrectomy. For patients in the GSP group, the second procedure was performed if there was inadequate improvement with the first procedure. There was no mortality. The follow-up period was 6-316 weeks (mean 66.107, SD 69.42). GES significantly improved frequency and severity for all symptoms except frequency of bloating and postprandial fullness. PP significantly improved nausea and vomiting severity, frequency of nausea, and early satiety. Symptom improvement for GSP was measured from after the first to after the second procedure. GSP significantly improved all but vomiting severity and frequency of early satiety, postprandial fullness, and epigastric pain., Conclusion: All procedures significantly improved symptoms, although numbers are small in the PP group. GES demonstrates more improvement than PP, and if PP or GES does not adequately improve symptoms GSP is appropriate. In our practice, gastrectomy was reserved as a last resort.

Bromodomain PHD finger transcription factor (BPTF) is the largest subunit of nucleosome remodeling factor (NURF), a member of the ISWI chromatin-remodeling complex. However, the clinical consequences of disruption of this complex remain largely uncharacterized. BPTF is required for anterior-posterior axis formation of the mouse embryo and was shown to promote posterior neuroectodermal fate by enhancing Smad2-activated wnt8 expression in zebrafish. Here, we report eight loss-of-function and two missense variants (eight de novo and two of unknown origin) in BPTF on 17q24.2. The BPTF variants were found in unrelated individuals aged between 2.1 and 13 years, who manifest variable degrees of developmental delay/intellectual disability (10/10), speech delay (10/10), postnatal microcephaly (7/9), and dysmorphic features (9/10). Using CRISPR-Cas9 genome editing of bptf in zebrafish to induce a loss of gene function, we observed a significant reduction in head size of F0 mutants compared to control larvae. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and phospho-histone H3 (PH3) staining to assess apoptosis and cell proliferation, respectively, showed a significant increase in cell death in F0 mutants compared to controls. Additionally, we observed a substantial increase of the ceratohyal angle of the craniofacial skeleton in bptf F0 mutants, indicating abnormal craniofacial patterning. Taken together, our data demonstrate the pathogenic role of BPTF haploinsufficiency in syndromic neurodevelopmental anomalies and extend the clinical spectrum of human disorders caused by ablation of chromatin remodeling complexes., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objectives: The American College of Emergency Physicians Geriatric Emergency Department (ED) Guidelines and the Center for Disease Control recommend that older adults be assessed for risk of falls. The standard ED assessment is a verbal query of fall risk factors, which may be inadequate. We hypothesized that the addition of a functional balance test endorsed by the Center for Disease Control Stop Elderly Accidents, Deaths, and Injuries Falls Prevention Guidelines, the 4-Stage Balance Test (4SBT), would improve the detection of patients at risk for falls., Methods: Prospective pilot study of a convenience sample of ambulatory adults 65 years and older in the ED. All participants received the standard nursing triage fall risk assessment. After patients were stabilized in their ED room, the 4SBT was administered., Results: The 58 participants had an average age of 74.1 years (range, 65-94), 40.0% were women, and 98% were community dwelling. Five (8.6%) presented to the ED for a fall-related chief complaint. The nursing triage screen identified 39.7% (n=23) as at risk for falls, whereas the 4SBT identified 43% (n=25). Combining triage questions with the 4SBT identified 60.3% (n=35) as at high risk for falls, as compared with 39.7% (n=23) with triage questions alone (P<.01). Ten (17%) of the patients at high risk by 4SBT and missed by triage questions were inpatients unaware that they were at risk for falls (new diagnoses)., Conclusions: Incorporating a quick functional test of balance into the ED assessment for fall risk is feasible and significantly increases the detection of older adults at risk for falls., Competing Interests: None reported., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Maternal uniparental disomy of chromosome 20 (UPD(20)mat) has been reported in only four patients, three of whom also had mosaicism for complete or partial trisomy of chromosome 20. We sought to evaluate the clinical significance of isolated UPD(20)mat in eight individuals., Methods: We evaluated phenotypic and genomic findings of a series of eight new patients with UPD(20)mat., Results: All eight individuals with UPD(20)mat had intrauterine growth restriction, short stature, and prominent feeding difficulties with failure to thrive. As a common feature, they often required gastric tube feeds. Genomic data in most patients are indicative of UPD as a result of trisomy rescue after meiosis II nondisjunction., Conclusion: We describe the first natural history of the disorder and the results of therapeutic interventions, including the frequent requirement of direct gastric feedings only during the first few years of life, and propose that growth hormone supplementation is probably safe and effective for this condition. We suggest that UPD(20)mat can be regarded as a new imprinting disorder and its identification requires specialized molecular testing, which should be performed in patients with early-onset idiopathic isolated growth failure.Genet Med 18 4, 309-315.

Filamin A (FLNA) is known to be involved in intracellular actin binding, cell migration, scaffolding, and signaling. We report a novel X-linked syndrome characterized by cardiac valvular disease, keloid scarring and reduced joint mobility in male second cousins due to a previously unreported mutation in FLNA. Whole exome sequencing was performed using standard methods and segregation analysis was performed in affected and non-affected family members. A novel hemizygous c.4726G>A (p.G1576R) mutation in FLNA was detected. Segregation analysis performed on multiple maternal family members showed c.4726G>A (p.G1576R) segregated with disease in an X-linked inheritance pattern. The findings in these cases are distinct from previously described FLNA related disorders by virtue of decreased joint mobility and spontaneous keloid scarring. They occur in association with a novel mutation and represent a novel genetic syndrome., (© 2015 Wiley Periodicals, Inc.)

Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from -2 SD to -5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype-phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs.

Noninvasive prenatal testing (NIPT) allows for highly sensitive detection of Down syndrome early in pregnancy with no risk of miscarriage, therefore potentially increasing the number of pregnancies identified with Down syndrome. This study assesses how mothers of children with Down syndrome perceive NIPT, especially the impact they think it will have on their families and other families with children who have Down syndrome. Seventy-three self-reported mothers of children with Down syndrome responded to an anonymous online survey emailed to, and posted on, message boards of various Down syndrome support groups and networks. Data analysis included chi-square tests and thematic analysis. Fifty-nine percent of respondents indicated they would use NIPT in the future; respondents who had not used prenatal testing in the past were significantly less likely to report interest in using NIPT in the future than those who had prenatal testing previously (p < .001). Many respondents felt NIPT could lead to increased terminations (88 %), increased social stigma (57 %), and decreased availability of services for individuals with Down syndrome (64 %). However, only 16 % believed availability of new noninvasive tests would be the most important factor in determining the number of pregnancies with Down syndrome terminated in the future. Additionally, 48 % believed health care providers give biased or incorrect information about Down syndrome at the time of diagnosis, and 24 % felt this incorrect information leads to terminations of pregnancies affected with Down syndrome. Results suggest although mothers of children with Down syndrome believe new noninvasive testing will lead to an increase in termination of pregnancies with Down syndrome, they do not think it is the MOST important factor. They also highlight the need to provide a diagnosis of Down syndrome in a balanced and objective manner.

Background: Clinical laboratories began offering whole-exome sequencing in 2011 at a cost between $4,500 and $9,000. Reported detection rates for deleterious mutations range from 25 to 50%. Based on the experience of our clinical genetics service, actual success rates may be lower than estimated rates. We report results from our own experience along with a survey of clinical geneticists to ascertain (i) current success rates for causal gene detection in a clinical setting; (ii) if there are insurance authorization issues; and (iii) if turnaround times quoted by the clinical laboratories are accurate; we also gauge provider opinions toward clinical whole-exome sequencing., Methods: We reviewed our results and the results of a survey that was electronically distributed to 47 clinical genetics centers., Results: A total of 35 exome reports were available. If all positive results are collated, we observe a success rate of 22.8%. One result incorrectly identified a known benign variant as pathogenic. Some insurers covered all testing, whereas others denied any insurance coverage. Only three (23.1%) of our reports were available within the laboratory's quoted turnaround times. More than 50% of clinicians queried in our survey had not ordered whole-exome sequencing at the current time, many stating concerns regarding interpretation, insurance coverage, and cost., Conclusion: Clinical whole-exome sequencing has proven diagnostic utility; however, currently many clinicians have concerns regarding interpretation of results, insurance coverage, and cost.

The Arlington County Wastewater Pollution Control Plant (ACWPCP) is located in the southern part of Arlington County, Virginia, USA and discharges to the Potomac River via the Four Mile Run. The ACWPCP was originally constructed in 1937. In 2001, Arlington County, Virginia (USA) committed to expanding their 113,500 m³/d, (300,000 pe) secondary treatment plant to a 151,400 m³/d (400,000 pe) to achieve effluent total nitrogen (TN) to <3 mg/l and total phosphorus (TP) < 0.18 mg/l. Key to this conversion was the implementation of deep bed denitrification filters to simultaneously achieve both low effluent TN and TP concentrations. A challenge with implementing this technology is maintaining a health denitrifying biomass within the denitrification filters while reducing an essential nutrient, phosphorus, to very low concentrations. This paper will review the steps from concept to the first year of operation, including pilot and full-scale operating data and the capital cost for the denitrification filters.

Background: The recently sequenced genome of Lactobacillus helveticus DPC4571 revealed a dairy organism with significant homology (75% of genes are homologous) to a probiotic bacteria Lb. acidophilus NCFM. This led us to hypothesise that a group of genes could be determined which could define an organism's niche., Results: Taking 11 fully sequenced lactic acid bacteria (LAB) as our target, (3 dairy LAB, 5 gut LAB and 3 multi-niche LAB), we demonstrated that the presence or absence of certain genes involved in sugar metabolism, the proteolytic system, and restriction modification enzymes were pivotal in suggesting the niche of a strain. We identified 9 niche specific genes, of which 6 are dairy specific and 3 are gut specific. The dairy specific genes identified in Lactobacillus helveticus DPC4571 were lhv&#95;1161 and lhv&#95;1171, encoding components of the proteolytic system, lhv&#95;1031 lhv&#95;1152, lhv&#95;1978 and lhv&#95;0028 encoding restriction endonuclease genes, while bile salt hydrolase genes lba&#95;0892 and lba&#95;1078, and the sugar metabolism gene lba&#95;1689 from Lb. acidophilus NCFM were identified as gut specific genes., Conclusion: Comparative analysis revealed that if an organism had homologs to the dairy specific geneset, it probably came from a dairy environment, whilst if it had homologs to gut specific genes, it was highly likely to be of intestinal origin.We propose that this "barcode" of 9 genes will be a useful initial guide to researchers in the LAB field to indicate an organism's ability to occupy a specific niche.

Mobile genetic elements are major contributing factors to the generation of genetic diversity in prokaryotic organisms. For example, insertion sequence (IS) elements have been shown to specifically contribute to niche adaptation by promoting a variety of genetic rearrangements. The complete genome sequence of the cheese culture Lactobacillus helveticus DPC 4571 was determined and revealed significant conservation compared to three nondairy gut lactobacilli. Despite originating from significantly different environments, 65 to 75% of the genes were conserved between the commensal and dairy lactobacilli, which allowed key niche-specific gene sets to be described. However, the primary distinguishing feature was 213 IS elements in the DPC 4571 genome, 10 times more than for the other lactobacilli. Moreover, genome alignments revealed an unprecedented level of genome stability between these four Lactobacillus species, considering the number of IS elements in the L. helveticus genome. Comparative analysis also indicated that the IS elements were not the primary agents of niche adaptation for the L. helveticus genome. A clear bias toward the loss of genes reported to be important for gut colonization was observed for the cheese culture, but there was no clear evidence of IS-associated gene deletion and decay for the majority of genes lost. Furthermore, an extraordinary level of sequence diversity exists between copies of certain IS elements in the DPC 4571 genome, indicating they may represent an ancient component of the L. helveticus genome. These data suggest a special unobtrusive relationship between the DPC 4571 genome and its mobile DNA complement.

Questionably viable skin flaps may be used as full thickness grafts after mastectomy. It is suggested that the procedure described can help reduce the incidence of flap necrosis after mastectomy and yield a more acceptable cosmetic result.

At the New York University Medical Center from January, 1969, through December, 1973, esophagogastrostomies were performed in 56 patients. In 30 (Group A), fundoplications were combined with the esophagogastrostomies; in the other 26 (Group B), esophagogastrostomies only were performed. These two groups have been compared in an effort to determine the effectiveness of fundoplication in preventing gastric reflux following esophagogastrostomy. The operative mortality rate (10 per cent) and the 3 year survival rate (20 per cent) were approximately equal in the two groups. Clinical evidence of reflux was noted in 10 per cent of Group A and 47 per cent of Group B patients, while complications of reflux were noted in 5 per cent of Group A and in 33 per cent of Group B patients. The results of the present study suggest that fundoplication, while not prolonging survival, does prevent the symptoms and complications of gastric reflux and improves the quality of survival in these unfortunate patients. This leads us to recommend the routine use of fundoplication with esophagogastrostomy in patients with carcinoma of the esophagus and gastric cardia.

A case of carcinoma of the jejunum occurring in a patient with Crohn's disease of 30-years' duration is presented. Forty-seven previously reported small bowel carcinomas in Crohn's disease patients are reviewed. The incidence of small bowel carcinomas in patients with Crohn's disease has been cited as being as low as 0.08%, a figure which is still higher than the 1 in 10(9) population which would be predicted if the two diseases were independent of one another. The average age of incidence of the Crohn's carcinomas was 46.5 years while that for the de novo group was 55 years. The sexual ratios were 2.46:1 and 2:1, males to females, for the respective groups. The de novo carcinomas had a slight predilection for the duodenum at 40.7% while the latter group had a heavy predilection for the ileum at 70.8% and contained no duodenal carcinomas. The prognosis of the Crohn's group appeared to be much worse than that of the de novo group with five-year survivals of 3.7% and 20-22% respectively. Late diagnosis in the enteritis group was felt to be the major reason for this. Finally, several pathological differences between the lesions in both groups are presented.