Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.

Somatosensory over-reactivity is common among patients with autism spectrum disorders (ASDs) and is hypothesized to contribute to core ASD behaviors. However, effective treatments for sensory over-reactivity and ASDs are lacking. We found distinct somatosensory neuron pathophysiological mechanisms underlie tactile abnormalities in different ASD mouse models and contribute to some ASD-related behaviors. Developmental loss of ASD-associated genes Shank3 or Mecp2 in peripheral mechanosensory neurons leads to region-specific brain abnormalities, revealing links between developmental somatosensory over-reactivity and the genesis of aberrant behaviors. Moreover, acute treatment with a peripherally restricted GABAA receptor agonist that acts directly on mechanosensory neurons reduced tactile over-reactivity in six distinct ASD models. Chronic treatment of Mecp2 and Shank3 mutant mice improved body condition, some brain abnormalities, anxiety-like behaviors, and some social impairments but not memory impairments, motor deficits, or overgrooming. Our findings reveal a potential therapeutic strategy targeting peripheral mechanosensory neurons to treat tactile over-reactivity and select ASD-related behaviors.

C9orf72 suppresses systemic and neural inflammation induced by gut bacteria.

A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3-9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6-9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.

The Role of Imaging for Gastrointestinal Bleeding: Consensus Recommendations From the American College of Gastroenterology and Society of Abdominal Radiology.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high healthcare utilization and costs. Radiologic techniques including computed tomography angiography, catheter angiography, computed tomography enterography, magnetic resonance enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided.

The Role of Imaging for GI Bleeding: ACG and SAR Consensus Recommendations.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high health care utilization and costs. Radiologic techniques including CT angiography, catheter angiography, CT enterography, MR enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist, which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided. © Radiological Society of North America and the American College of Gastroenterology, 2024. Supplemental material is available for this article. This article is being published concurrently in American Journal of Gastroenterology and Radiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Citations from either journal can be used when citing this article. See also the editorial by Lockhart in this issue.

Biallelic loss-of-function variants in CACHD1 cause a novel neurodevelopmental syndrome with facial dysmorphism and multisystem congenital abnormalities.

PURPOSE: We established the genetic etiology of a syndromic neurodevelopmental condition characterized by variable cognitive impairment, recognizable facial dysmorphism, and a constellation of extra-neurological manifestations. METHODS: We performed phenotypic characterization of 6 participants from 4 unrelated families presenting with a neurodevelopmental syndrome and used exome sequencing to investigate the underlying genetic cause. To probe relevance to the neurodevelopmental phenotype and craniofacial dysmorphism, we established two- and three-dimensional human stem cell-derived neural models and generated a stable cachd1 zebrafish mutant on a transgenic cartilage reporter line. RESULTS: Affected individuals showed mild cognitive impairment, dysmorphism featuring oculo-auriculo abnormalities, and developmental defects involving genitourinary and digestive tracts. Exome sequencing revealed biallelic putative loss-of-function variants in CACHD1 segregating with disease in all pedigrees. RNA sequencing in CACHD1-depleted neural progenitors revealed abnormal expression of genes with key roles in Wnt signaling, neurodevelopment, and organ morphogenesis. CACHD1 depletion in neural progenitors resulted in reduced percentages of post-mitotic neurons and enlargement of 3D neurospheres. Homozygous cachd1 mutant larvae showed mandibular patterning defects mimicking human facial dysmorphism. CONCLUSION: Our findings support the role of loss-of-function variants in CACHD1 as the cause of a rare neurodevelopmental syndrome with facial dysmorphism and multisystem abnormalities.

Imaging of Fontan-Associated Liver Disease.

ABSTRACT: The Fontan procedure is the definitive treatment for patients with single-ventricle physiology. Surgical advances have led to a growing number of patients surviving into adulthood. Fontan-associated liver disease (FALD) encompasses a spectrum of pathologic liver changes that occur secondary to altered physiology including congestion, fibrosis, and the development of liver masses. Assessment of FALD is difficult and relies on using imaging alongside of clinical, laboratory, and pathology information. Ultrasound, computed tomography, and magnetic resonance imaging are capable of demonstrating physiologic and hepatic parenchymal abnormalities commonly seen in FALD. Several novel imaging techniques including magnetic resonance elastography are under study for use as biomarkers for FALD progression. Imaging has a central role in detection and characterization of liver masses as benign or malignant. Benign FNH-like masses are commonly encountered; however, these can display atypical features and be mistaken for hepatocellular carcinoma (HCC). Fontan patients are at elevated risk for HCC, which is a feared complication and has a poor prognosis in this population. While imaging screening for HCC is widely advocated, no consensus has been reached regarding an optimal surveillance regimen.

Preferences of support and barriers and facilitators to help-seeking in pregnant women with severe fear of childbirth in Sweden: a mixed-method study.

BACKGROUND: There are few support interventions for women with fear of childbirth tailored towards type of fears and parity. To inform the future development of an acceptable and relevant intervention for women with severe fear of childbirth, primary objectives were to examine: (1) pregnant women's experiences of and preferences for support and (2) barriers and facilitators to help-seeking. Secondary objectives were to examine if there are any differences based on pregnant women's parity. METHODS: Pregnant women with a severe fear of childbirth in Sweden completed an online cross-sectional survey between February and September 2022. Severe fear of childbirth was measured using the fear of childbirth scale. Quantitative data were analysed using descriptive and inferential statistics and free answers were analysed using manifest content analysis. A contiguous approach to integration was adopted with qualitative and quantitative findings reported separately. RESULTS: In total, 609 participants, 364 nulliparous and 245 parous women, had severe fear of childbirth. The main category "A twisting road to walk towards receiving support for fear of childbirth" was explored and described by the generic categories: Longing for support, Struggling to ask for support, and Facilitating aspects of seeking support. Over half (63.5%), of pregnant women without planned or ongoing treatment, wanted support for fear of childbirth. Most (60.2%) pregnant women with ongoing or completed fear of childbirth treatment regarded the treatment as less helpful or not at all helpful. If fear of childbirth treatment was not planned, 35.8% of women would have liked to have received treatment. Barriers to help seeking included stigma surrounding fear of childbirth, previous negative experiences with healthcare contacts, fear of not being believed, fear of not being listened to, and discomfort of having to face their fears. Facilitators to help seeking included receiving respectful professional support that was easily available, flexible, and close to home. CONCLUSIONS: Most pregnant women with severe fear of childbirth felt unsupported during pregnancy. Findings emphasise the need to develop individual and easily accessible psychological support for women with severe fear of childbirth, delivered by trained professionals with an empathetic and respectful attitude.

Lack of patient and primary care physician follow-up in geriatric emergency department patients with head trauma from a fall.

STUDY OBJECTIVE: Falls are the leading cause of injuries in the US for older adults. Follow-up after an ED-related fall visit is essential to initiate preventive strategies in these patients who are at very high risk for recurrent falls. It is currently unclear how frequently follow-up occurs and whether preventive strategies are implemented. Our objective is to determine the rate of follow-up by older adults who sustain a fall related head injury resulting in an ED visit, the rate and type of risk assessment and adoption of preventive strategies. METHODS: This 1-year prospective observational study was conducted at two South Florida hospitals. All older ED patients with an acute head injury due to a fall were identified. Telephone surveys were conducted 14 days after ED presentation asking about PCP follow-up and adoption of fall prevention strategies. Clinical and demographic characteristics were compared between patients with and without follow up. RESULTS: Of 4951 patients with a head injury from a fall, 1527 met inclusion criteria. 905 reported follow-up with their PCP. Of these, 72% reported receiving a fall assessment and 56% adopted a fall prevention strategy. Participants with PCP follow-up were significantly more likely to have a history of cancer or hypertension. CONCLUSION: Only 60% of ED patients with fall-related head injury follow-up with their PCP. Further, 72% received a fall assessment and only 56% adopted a fall prevention strategy. These data indicate an urgent need to promote PCP fall assessment and adoption of prevention strategies in these patients.

Imaging of Bowel Ischemia: An Update, From the AJR Special Series on Emergency Radiology.

Acute mesenteric ischemia is a life-threatening condition that results from abrupt reduction in or cessation of blood flow to the bowel. Characterized by nonspecific abdominal symptoms, mesenteric ischemia is infrequently encountered and commonly misdiagnosed, with potentially catastrophic consequences. Prompt clinical diagnosis and early implementation of therapeutic interventions are critical to improving patient outcomes. Because cross-sectional imaging plays a key role in the diagnosis of mesenteric ischemia, radiologists must be familiar with the varied imaging manifestations of intestinal ischemia. Thus, the objectives of this article are to review the various types and common causes of mesenteric ischemia and to describe its spectrum of multimodality imaging findings, with special attention to novel imaging techniques and emerging diagnoses.

Dual-Energy CT Evaluation of Gastrointestinal Bleeding.

Gastrointestinal (GI) bleeding is a potentially life-threatening condition accounting for more than 300 000 annual hospitalizations. Multidetector abdominopelvic CT angiography is commonly used in the evaluation of patients with GI bleeding. Given that many patients with severe overt GI bleeding are unlikely to tolerate bowel preparation, and inpatient colonoscopy is frequently limited by suboptimal preparation obscuring mucosal visibility, CT angiography is recommended as a first-line diagnostic test in patients with severe hematochezia to localize a source of bleeding. Assessment of these patients with conventional single-energy CT systems typically requires the performance of a noncontrast series followed by imaging during multiple postcontrast phases. Dual-energy CT (DECT) offers several potential advantages for performing these examinations. DECT may eliminate the need for a noncontrast acquisition by allowing the creation of virtual noncontrast (VNC) images from contrast-enhanced data, affording significant radiation dose reduction while maintaining diagnostic accuracy. VNC images can help radiologists to differentiate active bleeding, hyperattenuating enteric contents, hematomas, and enhancing masses. Additional postprocessing techniques such as low-kiloelectron voltage virtual monoenergetic images, iodine maps, and iodine overlay images can increase the conspicuity of contrast material extravasation and improve the visibility of subtle causes of GI bleeding, thereby increasing diagnostic confidence and assisting with problem solving. GI bleeding can also be diagnosed with routine single-phase DECT scans by constructing VNC images and iodine maps. Radiologists should also be aware of the potential pitfalls and limitations of DECT. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Distinguishing Authentic Voices in the Age of ChatGPT: Comparing AI-Generated and Applicant-Written Personal Statements for Plastic Surgery Residency Application.

BACKGROUND: ChatGPT, a generative artificial intelligence model, may be used by future applicants in the plastic surgery residency match. METHODS: Ten personal statements (5 generated by ChatGPT, 5 written by applicants) were rated by 10 reviewers, blinded to the source of the essay. RESULTS: A total of a 100 evaluations were collected. There was no significant difference in ratings for readability, originality, authenticity, and overall quality (all P > 0.05) when comparing computer-generated and applicant essays. CONCLUSION: Personal statements prepared by ChatGPT are indistinguishable from essays written by actual applicants. This finding suggests that the current plastic surgery application format be reevaluated to better aid in holistic evaluation of students.

Midwives and child health nurses' support is associated with positive coparenting for fathers of infants: A cross-sectional analysis.

AIMS AND OBJECTIVES: To examine if the professional support that fathers received from midwives and child health nurses was associated with improvements in fathers' coparenting. A secondary aim was to investigate if there were any support differences between fathers based on parity. BACKGROUND: Stronger coparenting is associated with improved maternal, paternal and child health. It is unclear if routine prenatal and postnatal professional support is associated with improved coparenting in fathers of infants. DESIGN: Cross-sectional online survey. METHODS: In total, 612 fathers of infants (aged 0-24 months) completed baseline data between November 2018 and March 2020. Socio-demographics, pregnancy control variables, social support, professional support, being invited to attend and attending three specific visits for fathers, respectively, and the fathers' coparenting relationship, using the Brief Coparenting Relationship Scale, were assessed. The STROBE checklist was used as the reporting guideline for this study. RESULTS: Fathers' attendance at child health visits, support from the prenatal and postnatal midwife, respectively, and total support from the child health nurse, are associated with more positive coparenting. Primiparous fathers reported more received social and professional support, as well as a more positive coparenting relationship than multiparous fathers. CONCLUSIONS: Receiving clinical support from both midwives and child health nurses is associated with fathers' positive coparenting. All fathers should be invited and encouraged to attend prenatal, postnatal and child health visits to further support their coparenting relationship. Relative to primiparous fathers, multiparous fathers may require targeted and additional clinical support regarding their coparenting relationship. RELEVANCE TO CLINICAL PRACTICE: With fathers becoming more involved in childrearing, having stronger coparenting skills can help them better adapt to their parental roles. Our findings help understand how routine professional support from midwives and child health nurses are experienced among new fathers and that multiparous fathers are in further need of coparenting support.

Frequency, Indications and Intraoperative Dynamics of Repositioning of the Lateral Crura of the Lower Lateral Cartilage: A 35-Year Experience.

BACKGROUND: Lower lateral cartilage repositioning (LLCR) is an effective technique that places the lateral crus in a newly created caudal pocket, and is utilized for a variety of indications including cephalic malposition, alar asymmetries and tip rotation/projection alteration. However, there is a relative sparsity in the literature regarding this procedure and the dynamic changes that it produces. In this study, we report our experience with LLCR in regard to its indications and related interplays. METHODS: Data from our institution were collected from the most recent 100 primary rhinoplasties, most recent 100 secondary rhinoplasties and all LLCRs performed. For each LLCR, patient demographics and concurrent surgical techniques were compiled. A descriptive analysis was performed for all cohorts, while Fischer's exact test was performed to compare the associations of categorical data for the respective sample sizes of the primary and secondary rhinoplasty cohorts. RESULTS: Overall, 127 patients underwent LLCR, with eleven (11%) LLCRs in the primary rhinoplasty cohort and twelve (12%) LLCRs in the secondary rhinoplasty cohort. The most common indication for LLCR was cephalic malposition, followed by over-projection and asymmetry of the lower lateral cartilages. Intraoperative observation of dynamic changes included invariable cephalic rotation of the tip, ability to precisely control the tip projection, drastic narrowing of the domal arch often minimizing the need for the transdomal suture, alar repositioning caudally, correction of alar retraction and more elegant tip definition. However, the external valve lost its strength on majority of LLCR patients, which required almost routine use of Gunter lateral crus strut. CONCLUSION: LLCR is a powerful and versatile tool that can be utilized in either primary or secondary rhinoplasty. Its transposition results in cephalic rotation of the tip, narrowing of the domal arch, caudal reposition of the alar rim and superior tip definition. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266.

The Versatile Role of Fat Injection During Various Genioplasties.

BACKGROUND: Fat injection has become increasingly popular in aesthetic surgery, but there is a sparsity of literature regarding its role during genioplasty. In this study, we present the largest series of patients receiving fat injections to the chin for various indications. METHODS: Data were collected from January 2016 to December 2021 for patients who underwent chin fat injection for a variety of chin refinements. Patients with chin fat injection were divided into isolated genioplasty with fat injection (CF), combined facial and chin fat injection (CFC) and combined chin fat injection and osseous genioplasty (CFG). Complication rates and reoperations were compared using Fischer's exact test between each cohort. RESULTS: 181 patients were included in final analysis, with 14 patients in CF cohort, 130 patients in CFC cohort, 24 patients in CFG cohort, and 13 patients who underwent genioplasty alone. Repeat fat injections were required in 17 (9.4%) patients overall, which included 14 patients (10.8%) of CFC subcohort and three patients (12.5%) of CFG subcohort (p > 0.05). No patients who underwent genioplasty alone or CF required reoperation. There were no significant differences in complications between genioplasty alone group (0%) in comparison to CF (7.1%; p = 1.00), CFC (6.2%; p = .53), or CFG cohorts (7.7%; p = 1.00). CONCLUSION: Fat injection can safely correct minor chin deficiency or asymmetry, as either an isolated procedure or in combination with osteotomies. Additionally, fat injection enables advancement of the caudal segment to achieve superior outcomes by preventing unaesthetic deepening of labiomental groove which will not be advanced during sliding osteotomy. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Common Dorsal Flaws Following Preservation Rhinoplasty: A Systemic Analysis.

BACKGROUND: There has recently been a resurgence of interest in preservation rhinoplasty (PR) for dorsal hump elimination or dorsal projection reduction. However, no studies have scrutinized aesthetic outcomes to identify common pattern of flaws seen in published images to aid those with ardent enthusiasm for this technique to become aware of the frequency of these flaws and find ways to reduce imperfections. METHODS: A systematic literature review was performed using search terms ("preservation" OR "let down", "push down") AND "rhinoplasty" on PubMed, Cochrane, SCOPUS, and EMBASE databases for studies between January 2000 and December 2022. Patient images from these studies were analyzed by three reviewers (MWW, IAC, and BG) for dorsal flaws. Raw interrater agreement percentage and Krippendorff's alpha were calculated to determine interrater reliability. A descriptive and comparative analysis with Fisher's exact test was performed for the aggregate data. RESULTS: There were 59 patient images with 464 views from 24 studies included for final analysis. Optimal dorsal aesthetic lines (DAL) were noted in 12 patients (20.3%), while optimal profile was observed in 15 patients (25.4%) (p = 0.66). Combined ideal front and profile view of dorsum was not observed on any patients. The most common flaws were DAL irregularities (n = 45; 78.0%), dorsal deviation (n = 32, 54.2%), and residual hump (n = 25, 42.4%). There was excellent interrater agreement. CONCLUSIONS: While PR may have some advantages, it has shortcomings in outcomes, particularly dorsal irregularities, dorsal deviation, and residual humps. Awareness of these imperfections may compel those performing this procedure to modify their techniques and improve their results. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Logical Sequence of Primary Open Rhinoplasty Founded on the Principles of Rhinoplasty Dynamics.

Rhinoplasty is a perplexing procedure due to the variety of complex interplays between anatomical structures of the nose and the maneuvers used to accomplish the intended objective. Although every rhinoplasty is individualized, having a systematic order and an algorithm is crucial to achieve the designed aesthetic goals and a superior outcome, considering the interactions between maneuvers. Otherwise, the accumulated, unanticipated effects will result in displeasing outcomes due to over or under correction. In this report, we describe the sequential steps of rhinoplasty based on knowledge that the senior author has garnered over four decades of experience and having studied the rhinoplasty dynamics continually. Furthermore, we explain the detailed reasoning for each maneuver based on surgical indications and the resulting interplays.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Exploring the Resurgence of the Preservation Rhinoplasty: A Systematic Literature Review.

INTRODUCTION: The underlying principles of preservation rhinoplasty (PR) center around maintaining the soft tissue envelope, dorsum, and alar cartilage through surgical manipulations and tip suture techniques. In particular, the let-down (LD) and push-down (PD) techniques have been described, although reports of indications and outcomes in the literature are sparse. METHODS: A systematic review of the literature was performed using search terms "preservation" OR "let down" OR "push down" AND "rhinoplasty" on PubMed, Cochrane, SCOPUS, and EMBASE databases. Patient demographic information, operative details, and surgical outcomes were recorded. Sub-cohorts for patients who underwent LD and PD techniques were analyzed utilizing Fischer's exact test for categorical variables and Student's t test for continuous variables. RESULTS: Overall, there were 5967 PR patients in 30 studies in the final analysis, with 307 patients in the PD cohort and 529 patients in the LD cohort. The Rhinoplasty Outcome Evaluation Questionnaire showed a significant increase of patient satisfaction after PR compared to before PR (62.13 vs 91.14; p < 0.001). There was a significantly lower rate of residual dorsal hump or recurrence of 1.3% (n = 4) in the PD when compared to 4.6% (n = 23) in LD cohorts (p = 0.02). The revision rate of PD (0%, n = 0) was also significantly lower than that of LD (5.0%, n = 25) (p < 0.001). CONCLUSION: Based on these published articles, it seems that preservation rhinoplasty is safe and efficacious procedure with improved dorsal aesthetic lines, reduced dorsal contour irregularities, and claimed excellent patient satisfaction. In particular, the PD technique has fewer reported complications and revisions than LD approach, although PD is often indicated in patients with smaller dorsal humps. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

CrebA increases secretory capacity through direct transcriptional regulation of the secretory machinery, a subset of secretory cargo, and other key regulators.

Specialization of many cells, including the acinar cells of the salivary glands and pancreas, milk-producing cells of mammary glands, mucus-secreting goblet cells, antibody-producing plasma cells, and cells that generate the dense extracellular matrices of bone and cartilage, requires scaling up both secretory machinery and cell-type specific secretory cargo. Using tissue-specific genome-scale analyses, we determine how increases in secretory capacity are coordinated with increases in secretory load in the Drosophila salivary gland (SG), an ideal model for gaining mechanistic insight into the functional specialization of secretory organs. Our findings show that CrebA, a bZIP transcription factor, directly binds genes encoding the core secretory machinery, including protein components of the signal recognition particle and receptor, ER cargo translocators, Cop I and Cop II vesicles, as well as the structural proteins and enzymes of these organelles. CrebA directly binds a subset of SG cargo genes and CrebA binds and boosts expression of Sage, a SG-specific transcription factor essential for cargo expression. To further enhance secretory output, CrebA binds and activates Xbp1 and Tudor-SN. Thus, CrebA directly upregulates the machinery of secretion and additional factors to increase overall secretory capacity in professional secretory cells; concomitant increases in cargo are achieved both directly and indirectly.

Structure and Piezoelectricity Due to B Site Cation Variation in ABn+Cln+2 Hybrid Histammonium Chlorometallate Materials.

To provide new insights for understanding the influence of B site cations on the structure in chlorometallate materials of the form ABn+Cln+2, we report novel organic-inorganic hybrid metallates (OIHMs) incorporating histammonium (HistNH3) dications and various transition-metal and main group B site cations. Single crystals of OIHMs with the basic formula (HistNH3Mn+Cln+2, M = Fe, Co, Ni, Cu, Zn, Cd, Hg, Sb, Sn, Pb, Bi) were grown and their structures characterized by single-crystal X-ray crystallography. HistNH3CoCl4, HistNH3ZnCl4, and HistNH3SbCl5 were crystallized in a non-centrosymmetric space group and were subsequently studied with piezoresponse force microscopy (PFM). While bulk measurements of crystals and poly(vinylidene difluoride) (PVDF)/metallate composite films exhibited low bulk response values, the surface-measured local response values using PFM were 5.17 pm/V for HistNH3CoCl4, 22.6 pm/V for HistNH3ZnCl4, and 2.9 pm/V for HistNH3SbCl5 compared with 2.50 pm/V for PVDF reference samples. The magnitudes of the d33 coefficient, net dipole, and cation-Cl bond dipole obtained from the density functional theory calculations confirm the higher response in HistNH3ZnCl4 compared to HistNH3CoCl4. Density of states and crystal orbital Hamilton population analysis indicate that the higher net dipole in HistNH3ZnCl4 compared to HistNH3CoCl4 is due to the lower hybridization of the M-Cl bond.

Eosinophilic Disorders of the Gastrointestinal Tract and Associated Abdominal Viscera: Imaging Findings and Diagnosis.

Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions of the gastrointestinal tract that are characterized by tissue eosinophilia and end-organ dysfunction or damage. Primary EGIDs are associated with atopy and other allergic conditions, whereas secondary EGIDs are associated with underlying systemic diseases or hypereosinophilic syndrome. Within the spectrum of EGIDs, eosinophilic esophagitis is the most prevalent. Eosinophilic gastroenteritis and eosinophilic colitis are relatively uncommon. Eosinophilic infiltration of the liver, biliary tree, and/or pancreas also can occur and mimic other inflammatory and malignant conditions. Although endoscopic evaluation is the method of choice for eosinophilic esophagitis, radiologic evaluation of the esophagus plays an important role in the assessment of disease severity. CT and MR enterography are the modalities of choice for demonstrating specific forms of eosinophilic gastroenteritis. CT and MRI are important in the detection of abdominal visceral involvement in EGIDs. Diagnosis is often challenging and relies on symptoms, imaging findings, histologic confirmation of tissue eosinophilia, and correlation with peripheral eosinophilia. Imaging is crucial for identifying characteristic organ-specific findings, although imaging findings are not specific. When promptly treated, EGIDs usually have a benign clinical course. However, a delayed diagnosis and associated surgical interventions have been associated with morbidity. Therefore, a radiologist's knowledge of the imaging findings of EGIDs in the appropriate clinical settings may aid in early diagnosis and thereby improve patient care. An overview of the clinical features and imaging findings of EGIDs and the eosinophilic disorders of associated abdominal viscera is provided. Online supplemental material is available for this article. ©RSNA, 2022.