Individual Glands Research Articles

Impact of lead exposure on the thyroid glands of individuals living in high- or low-lead exposure areas.

Ecuador was an endemic area for iodine deficiency; however, due to the population consumption of iodized table salt, the country is nowadays considered iodine sufficient. Despite the population consumption of iodized salt for more than 50 years, the prevalence of hypothyroidism has increased in recent years. A similar increment has been reported for thyroid cancer (TC) becoming the second most common cancer in women and seventh most common cancer in men. High blood lead (BPb) level is a controversial causal factor for impaired thyroid function as well as a debated environmental cause for the increased incidence of TC. To study the association between BPb and thyroid function, anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies, and the presence of benign and malignant thyroid nodules in Ecuadorian individuals living in high lead exposure (HE) areas compared with those living in low lead exposure (LE) area. We evaluated 197 euthyroid individuals: 70 from Esmeraldas (close to a petrol refinery) and 27 from La Victoria de Pujilí (Pb-glazing ceramics), considered HE areas, and 100 from Quito, considered the LE area. In parallel, we evaluated 187 patients with hypothyroidism (60, 27, and 100 patients from Esmeraldas, Pujilí, and Quito, respectively). BPb was detected using atomic absorption spectroscopy, while thyroid-stimulating hormone (TSH), free-thyroxine (FT4), and autoantibodies were measured using chemiluminescence assays. Thyroid ultrasonography was performed in 300 individuals and fine-needle aspiration biopsy (FNA) was performed only when required based on the guidelines of the American Thyroid Association. The BPb levels (mean ± SD) in the HE areas were increased (8.5 ± 7.4) than those in the LE area (3.2 ± 2.4, P < .001). No significant associations were observed between BPb and TSH, FT4, or thyroid antibody levels. Enlarged thyroid glands and larger thyroid nodules were primarily observed in HE areas. Just 1 TC was observed. High BPb levels detected in HE areas were not associated with thyroid function or thyroid autoantibodies; however, increased thyroid size and numbers of thyroid nodules were observed, demanding further actions to control lead contamination in these Ecuadorian areas.

5-Hydroxytryptophan inhibits β-casein biosynthesis and promotes goat mammary epithelial cell apoptosis through the JAK2/STAT5a axis and the HTR7.

5-Hydroxytryptamine (5-HT) is an amine produced in both the mammary gland and the central nervous system. Tryptophan hydroxylase 1 (TPH1) catalyzes the conversion of 5-hydroxytryptophan (5-HTP) into l-tryptophan, which is then converted into 5-HT by monoamine-oxidase (MAO-A). In the mammary gland, 5-HT has been shown to have a variety of paracrine-autocrine actions, including suppressing lactation, controlling the destiny of mammary epithelial cells, and maintaining calcium homeostasis throughout the transition from pregnancy to lactation. To examine the effects of 5-HT on the composition of colostrum and milk, a total of 30 transition Guan Zhong dairy goats were intramuscularly injected with 5-HTP (1.0 mg/kg) every morning before feeding from 10 d before the projected parturition date to the day of parturition. The average number of days animals received injections was 8.2 ± 3.2 d. 5-HTP treatment increased serum 5-HT concentration from days 5 to 2 relative to parturition (P < 0.05), and decreased the casein concentration of colostrum (P < 0.05). In the in vitro experiment, mammary epithelial cells isolated from three individual goats' mammary glands were separately treated with 200 μM 5-HTP, 30 μM PCPA (the specific inhibitor of TPH1), or 200 μM 5-HTP + 50 μM SB269970 (the selective antagonist of 5-HTR7). The results showed that 200 μM 5-HTP inhibited the expression of β-casein, downregulated the activity of the JAK2/ STAT5a signaling pathway, and promoted the apoptosis of goat mammary epithelial cells (GMECs) (P < 0.05). When GMECs were treated with 30 μM Four-chloro-dl-phenylalanine (PCPA), a specific inhibitor of 5-HT synthesis, the mRNA expression of STAT5a and the phosphorylated STAT5a protein level were upregulated. The 50 μM SB269970 treatment rescued the effects of 5-HTP on GMECs (P < 0.05). Taken together, the results indicated that 5-HTP exerted an inhibitory effect on β-casein synthesis and a proapoptotic effect in GMECs via HTR7 and the JAK2/STAT5a axis.

Leukocyte Chemotactic Factor 2 Amyloidosis (ALECT2) Distribution in a Mexican Population.

To assess the prevalence of leukocyte cell-derived chemotactic 2 (LECT2), its organ involvement, and its clinical association in autopsies from an ethnically biased population. The tissues from all autopsies of individuals diagnosed with amyloidosis were reassessed and typed for amyloid light chain (AL) amyloidosis, amyloid A (AA) amyloidosis, transthyretin amyloidosis (ATTR), and leukocyte chemotactic factor 2 amyloidosis (ALECT2) by immunohistochemistry. Organ involvement was described and correlated with its clinical associations. Of 782 autopsies, 27 (3.5%) had a confirmed diagnosis of amyloidosis. Of these, 14 (52%) corresponded to ALECT2, 5 (19%) to AL amyloidosis, 2 (7%) to ATTR amyloidosis, 1 (4%) to AA amyloidosis, and 5 (21%) as undetermined-type amyloidosis. The LECT2 amyloid deposits were found in the kidneys, liver, spleen, and adrenal glands in most individuals. Except for the kidneys, there were no clinical signs suggestive of amyloid deposition in most of the affected organs. LECT2 amyloidosis was not associated with the cause of death in any case. No cases had heart or brain involvement. Potential subclinical effects of amyloid deposition in organs such as adrenal glands and spleen require further study. This autopsy study confirms the high prevalence of LECT2 amyloidosis in the Mexican population, with frequent amyloid deposition in the kidneys, liver, spleen, and adrenal glands.

The co-evolution of the genome and epigenome in colorectal cancer

Colorectal malignancies are a leading cause of cancer-related death1 and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4–7. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,370 samples from 30 primary cancers and 8 concomitant adenomas and generated 1,207 chromatin accessibility profiles, 527 whole genomes and 297 whole transcriptomes. We found positive selection for DNA mutations in chromatin modifier genes and recurrent somatic chromatin accessibility alterations, including in regulatory regions of cancer driver genes that were otherwise devoid of genetic mutations. Genome-wide alterations in accessibility for transcription factor binding involved CTCF, downregulation of interferon and increased accessibility for SOX and HOX transcription factor families, suggesting the involvement of developmental genes during tumourigenesis. Somatic chromatin accessibility alterations were heritable and distinguished adenomas from cancers. Mutational signature analysis showed that the epigenome in turn influences the accumulation of DNA mutations. This study provides a map of genetic and epigenetic tumour heterogeneity, with fundamental implications for understanding colorectal cancer biology.

INTERPRETATION OF MORPHOLOGICAL PICTURE OBSERVED IN HISTOLOGICAL PREPARATIONS FROM THE POINT THE VIEW OF STEREOLOGY

The study of a biological microobject from the standpoint of three-dimensionality gives more correct and realistic vision. The study material included 8 preparations of the palatine and labial salivary glands of adult human individuals fixed in 4% glutaraldehyde solution in phosphate buffer (pH 7.4). Following pre-fixation, the object was cut into individual slices and fixed in a freshly prepared similar fixator adding 1% calcium chloride solution at 4 °C for 12 hours. The tissue was washed after the fixation and then processed according to the requirements for electron microscopy. Tissues enclosed in epoxy resin were used to obtain semi-thin series of histological sections for further graphic and plastic reconstruction of epithelial components (including tubular) glands. Semi-thin sections were stained with 0.1% toluidine blue in phosphate buffer with different pH (from 5.5 to 8.5). Spiral, corkscrew, tortuous, arched and other forms of biological tubular structures at the microscopic level are no exception and, as our study shows, are natural phenomena along with their rectilinear shape. It can be assumed that the interdependence between the shape of the tubular transport microchannels and the laminar motion of the fluid naturally reflects the elements of curvilinear symmetry and, in particular, its spiral property. Conclusion. Thus, we could assume that the tortuous shape of transport channels of human and animal tissues is a useful stereomorphological device, and their study and three-dimensional modelling is of great scientific interest, in particular, for understanding the mechanism of laminar fluid movement through biological tubes.

Clinical Translationality of KCNJ5 Mutation in Aldosterone Producing Adenoma.

Hypertension due to primary aldosteronism poses a risk of severe cardiovascular complications compared to essential hypertension. The discovery of the KCNJ5 somatic mutation in aldosteroene producing adenoma (APA) in 2011 and the development of specific CYP11B2 antibodies in 2012 have greatly advanced our understanding of the pathophysiology of primary aldosteronism. In particular, the presence of CYP11B2-positive aldosterone-producing micronodules (APMs) in the adrenal glands of normotensive individuals and the presence of renin-independent aldosterone excess in normotensive subjects demonstrated the continuum of the pathogenesis of PA. Furthermore, among the aldosterone driver mutations which incur excessive aldosterone secretion, KCNJ5 was a major somatic mutation in APA, while CACNA1D is a leading somatic mutation in APMs and idiopathic hyperaldosteronism (IHA), suggesting a distinctive pathogenesis between APA and IHA. Although the functional detail of APMs has not been still uncovered, its impact on the pathogenesis of PA is gradually being revealed. In this review, we summarize the integrated findings regarding APA, APM or diffuse hyperplasia defined by novel CYP11B2, and aldosterone driver mutations. Following this, we discuss the clinical implications of KCNJ5 mutations to support better cardiovascular outcomes of primary aldosteronism.

A Simple Non-Contact Optical Method to Quantify In-Vivo Sweat Gland Activity and Pulsation.

Most methods for monitoring sweat gland activity use simple gravimetric methods, which merely measure the average sweat rate of multiple sweat glands over a region of skin. It would be extremely useful to have a method which could quantify individual gland activity in order to improve the treatment of conditions which use sweat tests as a diagnostic tool, such as hyperhidrosis, cystic fibrosis, and peripheral nerve degeneration. An optical method using an infrared camera to monitor the skin surface temperature was developed. A thermodynamics computer model was then implemented to utilize these skin temperature values along with other environmental parameters, such as ambient temperature and relative humidity, to calculate the sweat rates of individual glands using chemically stimulated and unstimulated sweating. The optical method was also used to monitor sweat pulsation patterns of individual sweat glands. In this preliminary study, the feasibility of the optical approach was demonstrated by measuring sweat rates of individual glands at various bodily locations. Calculated values from this method agree with expected sweat rates given values found in literature. In addition, a lack of pulsatile sweat expulsion was observed during chemically stimulated sweating, and a potential explanation for this phenomenon was proposed. A simple, non-contact optical method to quantify sweat gland activity in-vivo was presented. This method allows researchers and clinicians to investigate several sweat glands simultaneously, which has the potential to provide more accurate diagnoses and treatment as well as increase the potential utility for wearable sweat sensors.

High-throughput sequencing of IgH gene in minor salivary glands from Sjögren's syndrome patients reveals dynamic B cell recirculation between ectopic lymphoid structures.

B cells play a central role in Sjögren's syndrome (SS) whereby autoreactive B-cells populate ectopic germinal centres (GC) in SS salivary glands (SG) and undergo somatic hypermutation (SHM) and class-switch recombination of the immunoglobulin genes. However, the capacity of specific B cell clones to seed ectopic GC in different SG and undergo clonal diversification is unclear. To unravel the dynamics of B cell recirculation among minor SG biopsies, we investigated the immunoglobulin heavy chain (IgH) gene usage and the pattern of SHM using a high-throughput sequencing approach. We generated ~166,000 reads longer than 350bp and detected 1631 clonotypes across eight samples from four different SS patients, all characterised by the presence of functional ectopic GC as demonstrated by the expression of activation-induced cytidine deaminase. A large number of shared clonotypes were observed among paired mSG biopsies from each patient but not across different patients. Lineage tree analysis revealed significant clonal expansion within the mSG with the identification of shared dominant B cell clones suggestive of extensive recirculation across different SG. Several shared clonotypes with high proliferating capacity displayed IgH-VH gene usage common in autoreactive B cells, including VH1-69, which is typical of rheumatoid factor+ B cells representing potential lymphoma precursors. The complex dynamic recirculation of B cells that we observed within ectopic GC responses linked with their ability to independently proliferate, undergo ongoing SHM and Ig class-switching within individual glands may explain the difficulty in achieving consistent eradication of ectopic GCs following B cell depleting agents reported in different studies.

Pituitary Volume in Individuals with Social Anxiety Disorder.

There are no volumetric magnetic resonance imaging studies on the pituitary gland in individuals with social anxiety disorder. The present study aimed to investigate pituitary volume in individuals with social anxiety disorder compared to healthy controls due to the correlation between pituitary gland volume and stress response and the hypothalamic-pituitary-adrenal axis and hypothesized that pituitary gland volume would be different in these individuals. In this study, 21 individuals with social anxiety disorder based on fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and 20 healthy controls were included. Both patient and control groups were scanned with a 1.5-Tesla General Electric (GE) Magnetic Resonance Imaging scanner. Pituitary volume was measured with the manual tracing method. The statistical analysis revealed that the mean pituitary gland volume of the individuals with social anxiety disorder was significantly smaller when compared to that of healthy controls, statistically, as presented inTable 1 [594.10±104.56 mm3 for individuals with social anxiety disorder and 818.01±215.25 mm3 for healthy controls] when it was done by using the analysis of covariance controlled for age (F = 12.979, df = 1, P < .001), sex (F = 11.448, df = 1, P < .001), and total brain volume (F = 10.772, df = 1, P < .001), demonstrating that smaller pituitary volume in social anxiety disorder, when compared to healthy subjects, was an important finding independent of age, sex, or total brain volume. We suggest that social anxiety disorder may be associated with smaller pituitary volume, supporting the notion that anxiety itself could reduce the pituitary volume.

Parathyroid 4D CT in Primary Hyperparathyroidism: Exploration of Size Measurements for Identifying Multigland Disease and Guiding Biochemically Successful Parathyroidectomy.

BACKGROUND. In patients with primary hyperparathyroidism (PHPT), bilateral neck exploration is necessary for multigland disease (MGD), whereas minimally invasive parathyroidectomy is often preferred for single-gland disease (SGD). An existing system (the 4D-CT MGD score) for differentiating SGD from MGD with the use of preoperative parathyroid CT considers the size of only the largest candidate lesion. OBJECTIVE. The purpose of this study was to assess the utility of the size of the second-largest lesion on parathyroid CT for differentiating SGD from MGD as well as the utility of individual gland size for predicting the need for surgical removal and to derive optimal size thresholds for these purposes. METHODS. This retrospective study included patients with PHPT who underwent biochemically successful parathyroidectomy after preoperative parathyroid CT. Clinical radiology reports were reviewed to classify reported candidate parathyroid lesions as low-, intermediate-, or high-confidence lesions. Resected hypercellular parathyroid lesions were correlated with clinically reported candidate lesions. Patients were classified as having SGD or MGD on the basis of operative and pathology reports, independent of CT findings. One observer retrospectively determined the estimated volume (0.52 × length × width × height) and maximum diameter of clinically reported high-confidence lesions, as well as the 4D-CT MGD scores from the examinations. Diagnostic performance was assessed. RESULTS. The sample comprised 62 patients (41 women, 21 men; median age, 65 years), 47 of whom had SGD and 15 of whom had MGD, with 151 candidate lesions, including 106 high-confidence lesions. Based on the second-largest high-confidence lesions, an estimated volume threshold of 60 mm3 or greater achieved 53% sensitivity and 96% specificity, whereas a maximum diameter threshold of 7 mm or greater achieved 67% sensitivity and 96% specificity for MGD; a 4D-CT MGD score of 3 or greater achieved 47% sensitivity and 68% specificity for MGD. For predicting the need to remove a gland for successful parathyroidectomy, an estimated volume threshold of 114 mm3 or greater achieved 84% sensitivity and 97% specificity, and a threshold of 55 mm3 or greater achieved 93% sensitivity and 87% specificity; a maximum diameter threshold of 7 mm or greater achieved 93% sensitivity and 84% specificity. CONCLUSION. The estimated volume and maximum diameter of high-confidence candidate lesions can differentiate SGD from MGD and identify individual glands requiring removal for successful parathyroidectomy. Differentiating SGD from MGD may be aided by considering both the first- and second-largest high-confidence lesions. CLINICAL IMPACT. The findings will help identify patients who are likely to require bilateral neck explorations, informing preoperative patient counseling and individualized operative planning.

Morphological evaluation of the orbit, eye tunics, eyelids, and orbital glands in young and adult aardvarks Orycteropus afer, Pallas, 1766 (Tubulidentata: Orycteropodidae): Similarities and differences with representatives of the Afrotheria clade.

The Afrotheria clade includes a large group of extant mammals, and the aardvark (Orycteropus afer) is the only representative of the order Tubulidentata in it. Here, we studied the morphological nature of the orbital region, eye tunics, upper and lower eyelids, superficial gland of the third eyelid, the third eyelid, deep gland of the third eyelid, and lacrimal gland in post-mortem specimens obtained from three captive aardvarks, two young and one adult. The obtained samples were analyzed using macroscopic, histological, and histochemical methods. We observed choroidal tapetum lucidum fibrosum in all specimens, which was typical for aardvarks. The superficial gland of the third eyelid was a compound multilobar tubular branched gland of a mucous nature. The deep gland of the third eyelid produced a serous secretion. The seromucous secretion was typical for the lacrimal gland. We compared the morphological data of the O. afer skull with that from other endemic African mammals in the Afrotheria clade. We found that other authors provided different anatomical names for some bones and foramina located within the orbit. The types and function of eyelid glands, as well as eyeball glands of aardvarks, can primarily be connected with their habitat. Our study may constitute an introduction to the ontogenesis of individual eyeball glands in aardvarks.

A reproducible and sensitive method for generating high-quality transcriptomes from single whitefly salivary glands and other low-input tissues.

Transcriptomic studies are an important tool for understanding the molecular pathways underlying host plant use by agricultural pests, including vectors of damaging plant pathogens. Thus far, bulk RNA-Seq has been the main approach for non-model insects. This method relies on pooling large numbers of whole organisms or hundreds of individually dissected organs. The latter approach is logistically challenging, may introduce artifacts of handling and storage, and is not compatible with biological replication. Here, we tested an approach to generate transcriptomes of individual salivary glands and other low-input body tissues from whiteflies (Bemisia tabaci MEAM1), which are major vectors of plant viruses. By comparing our outputs to published bulk RNA-Seq datasets for whole whitefly bodies and pools of salivary glands, we demonstrate that this approach recovers similar numbers of transcripts relative to bulk RNA-Seq in a tissue-specific manner, and for some metrics, exceeds performance of bulk tissue RNA-Seq. Libraries generated from individual salivary glands also yielded additional novel transcripts not identified in pooled salivary gland datasets, and had hundreds of enriched transcripts when compared with whole head tissues. Overall, our study demonstrates that it is feasible to produce high quality, replicated transcriptomes of whitefly salivary glands and other low-input tissues. We anticipate that our approach will expand hypothesis-driven research on salivary glands of whiteflies and other Hemiptera, thus enabling novel control strategies to disrupt feeding and virus transmission.

Genetics of Primary Aldosteronism.

Primary aldosteronism is considered the commonest cause of secondary hypertension. In affected individuals, aldosterone is produced in an at least partially autonomous fashion in adrenal lesions (adenomas, [micro]nodules or diffuse hyperplasia). Over the past decade, next-generation sequencing studies have led to the insight that primary aldosteronism is largely a genetic disorder. Sporadic cases are due to somatic mutations, mostly in ion channels and pumps, and rare cases of familial hyperaldosteronism are caused by germline mutations in an overlapping set of genes. More than 90% of aldosterone-producing adenomas carry somatic mutations in K+ channel Kir3.4 (KCNJ5), Ca2+ channel CaV1.3 (CACNA1D), alpha-1 subunit of the Na+/K+ ATPase (ATP1A1), plasma membrane Ca2+ transporting ATPase 3 (ATP2B3), Ca2+ channel CaV3.2 (CACNA1H), Cl− channel ClC-2 (CLCN2), β-catenin (CTNNB1), and/or G-protein subunits alpha q/11 (GNAQ/11). Mutations in some of these genes have also been identified in aldosterone-producing (micro)nodules, suggesting a disease continuum from a single cell, acquiring a somatic mutation, via a nodule to adenoma formation, and from a healthy state to subclinical to overt primary aldosteronism. Individual glands can have multiple such lesions, and they can occur on both glands in bilateral disease. Familial hyperaldosteronism, typically with early onset, is caused by germline mutations in steroid 11-beta hydroxylase/ aldosterone synthase (CYP11B1/2), CLCN2, KCNJ5, CACNA1H, and CACNA1D.

Quantifying Meibomian Gland Morphology Using Artificial Intelligence.

Quantifying meibomian gland morphology from meibography images is used for the diagnosis, treatment, and management of meibomian gland dysfunction in clinics. A novel and automated method is described for quantifying meibomian gland morphology from meibography images. Meibomian gland morphological abnormality is a common clinical sign of meibomian gland dysfunction, yet there exist no automated methods that provide standard quantifications of morphological features for individual glands. This study introduces an automated artificial intelligence approach to segmenting individual meibomian gland regions in infrared meibography images and analyzing their morphological features. A total of 1443 meibography images were collected and annotated. The dataset was then divided into development and evaluation sets. The development set was used to train and tune deep learning models for segmenting glands and identifying ghost glands from images, whereas the evaluation set was used to evaluate the performance of the model. The gland segmentations were further used to analyze individual gland features, including gland local contrast, length, width, and tortuosity. A total of 1039 meibography images (including 486 upper and 553 lower eyelids) were used for training and tuning the deep learning model, whereas the remaining 404 images (including 203 upper and 201 lower eyelids) were used for evaluations. The algorithm on average achieved 63% mean intersection over union in segmenting glands, and 84.4% sensitivity and 71.7% specificity in identifying ghost glands. Morphological features of each gland were also fed to a support vector machine for analyzing their associations with ghost glands. Analysis of model coefficients indicated that low gland local contrast was the primary indicator for ghost glands. The proposed approach can automatically segment individual meibomian glands in infrared meibography images, identify ghost glands, and quantitatively analyze gland morphological features.

Does Dose Volume Histogram of Parotid Glands Correlate with Xerostomia Radiation Therapy Oncology Group Scores in Locoregionally Advanced Head and Neck Cancer Patients Treated with Intensity-Modulated Radiation Therapy?

Introduction Xerostomia is an imminent complication of head and neck radiotherapy best assessed subjectively. This study aimed to evaluate the effects of sparing parotid glands with intensity-modulated radiation therapy (IMRT) on subjective xerostomia scores in patients with locoregionally advanced head and neck cancer. Subjects and Methods This is a prospective longitudinal study conducted in an outpatient department setting. A total of 43 patients with head and neck cancer were planned with IMRT as per the ICRU 62 (International Commission on Radiation Units and Measurement Report 62). The constraints to ipsilateral and contralateral parotid glands were 35 and 25 Gy, respectively. Treatment plan was assessed for doses to 100, 67, 50, and 33% volume of individual parotid glands. Patients were subjectively assessed using the Amosson’s Questionnaire and graded as per Eisbruch’s xerostomia Radiation Therapy Oncology Group scores. Dose volume histogram (DVH) was plotted and correlated with grades of xerostomia postradiation at 1, 3, 6, 9 and 12 months follow-ups. Statistical analysis was performed suing SPSS version 16, chi-square test, and one-way analysis of variance test. Results No statistically significant correlation between mean dose of radiation, volume of the parotid glands, and grades of xerostomia was noted postradiation. A statistically significant improvement in grades of xerostomia between 3 and 6 months (p = 0.0), 3 and 9 months (p = 0.020), 6 and 9 months (p = 0.009), 6 and 12 months (p = 0.05), and 9 and 12 months (p = 0.00) was noted. Recovery in grades was noted at 9 months. Conclusion There is no statistically significant direct correlation between DVH of the parotid glands and grades of xerostomia, although recovery in grades was statistically significant at 9 months.

Preoperative Calcium and Parathyroid Hormone Values Are Poor Predictors of Gland Volume and Multigland Disease in Primary Hyperparathyroidism: A Review of 2000 Consecutive Patients

ObjectiveCalcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland size, with higher values predicting single-gland disease. In this modern series, these preoperative values were correlated with operative findings to determine their utility in predicting the gland involvement at parathyroid exploration. MethodsTwo thousand consecutive patients who underwent initial surgery for sporadic primary hyperparathyroidism from 2000 to 2014 were reviewed. All patients underwent a 4-gland exploration. Relationships between preoperative calcium and PTH values with the total gland volume of each patient were examined and stratified using the number of involved glands: single adenoma (SA), double adenoma (DA), and hyperplasia (H). ResultsThere were 1274 (64%) SA, 359 (18%) DA, and 367 (18%) H cases. There was a poor correlation between preoperative calcium and PTH values (R = 0.37) and both poorly correlated with the total gland volume (R < 0.40). Similarly, subgroup analysis using the number of involved glands showed poor correlation. The mean total gland volume was similar among all subgroups (SA = 1.28 cm3, DA = 1.43 cm3, and H = 1.27 cm3; P = .52), implying that individual glands were smaller in multigland disease. SA was found in 271 (53%) of patients with calcium levels of ≤10.5 mg/dL and 122 (78%) with levels of ≥12 mg/dL (P < .001). ConclusionThis is the largest series correlating preoperative calcium and PTH values with operative findings of gland size and number of diseased glands. Although a lower calcium value predicts somewhat more multigland disease, the overall poor correlation should make the parathyroid surgeon aware that gland size and multigland disease cannot be predicted by preoperative laboratory testing.

Single-cell analysis of mouse and human prostate reveals novel fibroblasts with specialized distribution and microenvironment interactions.

Stromal-epithelial interactions are critical to the morphogenesis, differentiation, and homeostasis of the prostate, but the molecular identity and anatomy of discrete stromal cell types is poorly understood. Using single-cell RNA sequencing, we identified and validated the in situ localization of three smooth muscle subtypes (prostate smooth muscle, pericytes, and vascular smooth muscle) and two novel fibroblast subtypes in human prostate. Peri-epithelial fibroblasts (APOD+) wrap around epithelial structures, whereas interstitial fibroblasts (C7+) are interspersed in extracellular matrix. In contrast, the mouse displayed three fibroblast subtypes with distinct proximal-distal and lobe-specific distribution patterns. Statistical analysis of mouse and human fibroblasts showed transcriptional correlation between mouse prostate (C3+) and urethral (Lgr5+) fibroblasts and the human interstitial fibroblast subtype. Both urethral fibroblasts (Lgr5+) and ductal fibroblasts (Wnt2+) in the mouse contribute to a proximal Wnt/Tgfb signaling niche that is absent in human prostate. Instead, human peri-epithelial fibroblasts express secreted WNT inhibitors SFRPs and DKK1, which could serve as a buffer against stromal WNT ligands by creating a localized signaling niche around individual prostate glands. We also identified proximal-distal fibroblast density differences in human prostate that could amplify stromal signaling around proximal prostate ducts. In human benign prostatic hyperplasia, fibroblast subtypes upregulate critical immunoregulatory pathways and show distinct distributions in stromal and glandular phenotypes. A detailed taxonomy of leukocytes in benign prostatic hyperplasia reveals an influx of myeloid dendritic cells, T cells and B cells, resembling a mucosal inflammatory disorder. A receptor-ligand interaction analysis of all cell types revealed a central role for fibroblasts in growth factor, morphogen, and chemokine signaling to endothelia, epithelia, and leukocytes. These data are foundational to the development of new therapeutic targets in benign prostatic hyperplasia. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A CASE REPORT OF CARCINOMA EX BASAL CELL ADENOMA OF THE PAROTID GLAND

<h3>Background</h3> Basal cell adenocarcinoma (BAC) is a rare salivary gland malignancy that occurs primarily in the parotid gland of elder individuals (median 60 years old) without a sex predilection. <h3>Objective</h3> To report a case of intracapsular malignant transformation of basal cell adenoma (BCA) into BAC, thus providing a reference for clinical work. <h3>Method</h3> A case of carcinoma ex BCA of the parotid gland was retrospectively analyzed. <h3>Results</h3> A 63⁃year⁃old female patient with a mass on the right side of the lower ear presented to our hospital. The clinical diagnosis tended to be a benign tumor. She received surgery, and the tumor underwent pathological examination. Microscopically, the tumor essentially showed characteristics of BCA composed of groups of basaloid cells. However, the tumor cells infiltrated the capsule, and malignant transformation occurred in some areas. The final diagnosis was basal cell carcinoma ex BCA. BAC is a malignant tumor composed of basal cell–like cells, which is similar to BCA in cytology and histopathology. The key point of differential diagnosis is whether the atypia of tumor cells and nuclear mitosis are easily seen and whether there is clear invasive growth. <h3>Conclusions</h3> Difficulty can be encountered in clinical manifestation and histologically in differential diagnosis of lesions such as BCA from BAC. As seen in the present case, the patient showed intracapsular malignant transformation of BCA into BAC. In the diagnosis of parotid masses in elderly patients, attention should be paid to the differentiation between BCA and BAC.

Ocean Warming May Enhance Biochemical Alterations Induced by an Invasive Seaweed Exudate in the Mussel Mytilus galloprovincialis.

Ocean warming and biological invasions are among the most pervasive factors threatening coastal ecosystems with a potential to interact. Ongoing temperature rise may affect physiological and cellular mechanisms in marine organisms. Moreover, non-indigenous species spread has been a major challenge to biodiversity and ecosystem functions and services. The invasive red seaweed Asparagopsis armata has become successfully established in Europe. Its exudate has been considered deleterious to surrounding native species, but no information exists on its effect under forecasted temperature increase. This study evaluated the combined effects of temperature rise and A. armata exudate exposure on the native mussel Mytilus galloprovincialis. Oxidative stress, neurophysiological and metabolism related biomarkers were evaluated after a 96 h-exposure to exudate (0% and 2%) under present (20 °C) and warming (24 °C) temperature scenarios. Short-term exposure to A. armata exudate affected the oxidative stress status and neurophysiology of the mussels, with a tendency to an increasing toxic action under warming. Significant oxidative damage at protein level was observed in the digestive gland and muscle of individuals exposed simultaneously to the exudate and temperature rise. Thus, under a climate change scenario, it may be expected that prolonged exposure to the combined action of both stressors may compromise M. galloprovincialis fitness and survival.

Optical Measurements of Sweat for in Vivo Quantification of CFTR Function in Individual Sweat Glands

Optical measurement of CFTR-dependent sweat secretion stimulated by a beta-adrenergic cocktail (C-phase) vs. CFTR-independent sweat secretion induced by methacholine (M-phase) can discriminate cystic fibrosis (CF) patientts from controls and healthy carriers by the ratio of sweat rate in the C-phase vs. the M-phase (C/M ratio). However, image analysis is experimentally demanding and time-consuming. Here, sweat droplet number (SDN) in the C-phase, corresponding to the number of sweat-secreting glands, was a statistically significant predictor for detecting the effects of CFTR-targeted therapy. We show that in 44 non-CF subjects and 110 CF patients, SDN in the C-phase provides a linear readout of CFTR function that is more sensitive than that using the C/M ratio. In CF patients, increased SDN in the C-phase during treatment with (LUMA/IVA) was associated with a trend toward improved lung function (FEV1). Our method is suitable for multicenter monitoring of the effects of CFTR modulators.