Histological assessment of microtia cartilage, a potential source of autograft tissue in ear reconstruction.

Cartilage is a strong and flexible connective tissue that has many forms and functions in our body. While cartilage exhibits some forms of limited repair, for the most part, it is not particularly regenerative. Thus, in situations where patients require cartilage reconstruction, surgeons may use autografts to replace missing or damaged tissue. Cartilage tissues from different regions of the body exhibit histological differences and are in limited supply. Thus, it is important to characterize these differences to determine the most appropriate autograft source. In the case of microtia, a congenital deformity where the pinna is underdeveloped, reconstruction commonly utilizes cartilage sourced from a patient's own costal cartilage. This presents a potential morbidity risk. In this study, we evaluate the histological characteristics of microtia cartilage compared with normal auricular and costal cartilage obtained from human patients undergoing surgical resection. Histochemistry was used to evaluate cellularity, lipid content, and ECM content. Using a Bayesian statistical approach, we determined that while costal cartilage is the standard tissue donor, the microanatomy of microtia cartilage more closely reflects normal auricular cartilage than costal cartilage. Therefore, microtia cartilage may serve as an additional reservoir for cartilage during reconstruction.

The effect of red blood cell disorders on male fertility and reproductive health.

Male infertility is defined as a failure to conceive after 12 months of unprotected intercourse owing to suspected male reproductive factors. Non-malignant red blood cell disorders are systemic conditions that have been associated with male infertility with varying severity and strength of evidence. Hereditary haemoglobinopathies and bone marrow failure syndromes have been associated with hypothalamic-pituitary-gonadal axis dysfunction, hypogonadism, and abnormal sperm parameters. Bone marrow transplantation is a potential cure for these conditions, but exposes patients to potentially gonadotoxic chemotherapy and/or radiation that could further impair fertility. Iron imbalance might also reduce male fertility. Thus, disorders of hereditary iron overload can cause iron deposition in tissues that might result in hypogonadism and impaired spermatogenesis, whereas severe iron deficiency can propagate anaemias that decrease gonadotropin release and sperm counts. Reproductive urologists should be included in the comprehensive care of patients with red blood cell disorders, especially when gonadotoxic treatments are being considered, to ensure fertility concerns are appropriately evaluated and managed.

Polygenic Risk Score Associates With Atherosclerotic Plaque Characteristics at Autopsy.

BACKGROUND: Polygenic risk scores (PRSs) for coronary artery disease (CAD) potentially improve cardiovascular risk prediction. However, their relationship with histopathologic features of CAD has never been examined systematically. METHODS: From 4327 subjects referred to CVPath by the State of Maryland Office Chief Medical Examiner for sudden death between 1994 and 2015, 2455 cases were randomly selected for genotyping. We generated PRS from 291 known CAD risk loci. Detailed histopathologic examination of the coronary arteries was performed in all subjects. The primary study outcome measurements were histopathologic plaque features determining severity of atherosclerosis, including %stenosis, calcification, thin-cap fibroatheromas, and thrombotic CAD. RESULTS: After exclusion of cases with insufficient DNA sample quality or with missing data, 954 cases (mean age, 48.8±14.7 years; 75.7% men) remained in the final study cohort. Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared with subjects in the lowest quintile, with greater %stenosis (80.3%±27.0% versus 50.4%±38.7%; adjusted P<0.001) and a higher frequency of calcification (69.6% versus 35.8%; adjusted P=0.004) and thin-cap fibroatheroma (26.7% versus 9.5%; adjusted P=0.007). Even after adjustment for traditional CAD risk factors, subjects within the highest PRS quintile had higher odds of severe atherosclerosis (ie, ≥75% stenosis; adjusted odds ratio, 3.77 [95% CI, 2.10-6.78]; P<0.001) and plaque rupture (adjusted odds ratio, 4.05 [95% CI, 2.26-7.24]; P<0.001). Moreover, subjects within the highest quintile had higher odds of CAD-associated cause of death, especially among those aged ≤50 years (adjusted odds ratio, 4.08 [95% CI, 2.01-8.30]; P<0.001). No statistically significant associations were observed with plaque erosion after adjusting for covariates. CONCLUSIONS: This is the first autopsy study investigating associations between PRS and atherosclerosis severity at the histopathologic level in subjects with sudden death. Our pathological analysis suggests PRS correlates with plaque burden and features of advanced atherosclerosis and may be useful as a method for CAD risk stratification, especially in younger subjects.

Polygenic Risk Score Associates with Atherosclerotic Plaque Characteristics at Autopsy.

Background: Polygenic risk scores (PRS) for coronary artery disease (CAD) potentially improve cardiovascular risk prediction. However, their relationship with histopathologic features of CAD has never been examined systematically. Methods: From 4,327 subjects referred to CVPath by the State of Maryland Office Chief Medical Examiner (OCME) for sudden death between 1994 and 2015, 2,455 cases were randomly selected for genotyping. We generated PRS from 291 known CAD risk loci. Detailed histopathologic examination of the coronary arteries was performed in all subjects. The primary study outcome measurements were histopathologic plaque features determining severity of atherosclerosis, including %stenosis, calcification, thin-cap fibroatheromas (TCFA), and thrombotic CAD. Results: After exclusion of cases with insufficient DNA sample quality or with missing data, 954 cases (mean age 48.8±14.7; 75.7% men) remained in the final study cohort. Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared to subjects in the lowest quintile, with greater %stenosis (80.3%±27.0% vs. 50.4%±38.7%; adjusted p<0.001) and a higher frequency of calcification (69.6% vs. 35.8%; adjusted p=0.004) and TCFAs (26.7% vs. 9.5%; adjusted p=0.007). Even after adjustment for traditional CAD risk factors subjects within the highest PRS quintile had higher odds of severe atherosclerosis (i.e., ≥75% stenosis; adjusted OR 3.77; 95%CI 2.10-6.78; p<0.001) and plaque rupture (adjusted OR 4.05; 95%CI 2.26-7.24; p<0.001). Moreover, subjects within the highest quintile had higher odds of CAD-associated cause of death, especially among those aged 50 years and younger (adjusted OR 4.08; 95%CI 2.01-8.30; p<0.001). No associations were observed with plaque erosion. Conclusions: This is the first autopsy study investigating associations between PRS and atherosclerosis severity at the histopathologic level in subjects with sudden death. Our pathological analysis suggests PRS correlates with plaque burden and features of advanced atherosclerosis and may be useful as a method for CAD risk stratification, especially in younger subjects. Highlights: In this autopsy study including 954 subjects within the CVPath Sudden Death Registry, high PRS correlated with plaque burden and atherosclerosis severity.The PRS showed differential associations with plaque rupture and plaque erosion, suggesting different etiologies to these two causes of thrombotic CAD.PRS may be useful for risk stratification, particularly in the young. Further examination of individual risk loci and their association with plaque morphology may help understand molecular mechanisms of atherosclerosis, potentially revealing new therapy targets of CAD. Graphic Abstract: A polygenic risk score, generated from 291 known CAD risk loci, was assessed in 954 subjects within the CVPath Sudden Death Registry. Histopathologic examination of the coronary arteries was performed in all subjects. Subjects in the highest PRS quintile exhibited more severe atherosclerosis as compared to subjects in the lowest quintile, with a greater plaque burden, more calcification, and a higher frequency of plaque rupture.

CD163+ macrophages restrain vascular calcification, promoting the development of high-risk plaque.

Vascular calcification (VC) is concomitant with atherosclerosis, yet it remains uncertain why rupture-prone high-risk plaques do not typically show extensive calcification. Intraplaque hemorrhage (IPH) deposits erythrocyte-derived cholesterol, enlarging the necrotic core and promoting high-risk plaque development. Pro-atherogenic CD163+ alternative macrophages engulf hemoglobin:haptoglobin (HH) complexes at IPH sites. However, their role in VC has never been examined to our knowledge. Here we show, in human arteries, the distribution of CD163+ macrophages correlated inversely with VC. In vitro experiments using vascular smooth muscle cells (VSMCs) cultured with HH-exposed human macrophage - M(Hb) - supernatant reduced calcification, while arteries from ApoE-/- CD163-/- mice showed greater VC. M(Hb) supernatant-exposed VSMCs showed activated NF-κB, while blocking NF-κB attenuated the anticalcific effect of M(Hb) on VSMCs. CD163+ macrophages altered VC through NF-κB-induced transcription of hyaluronan synthase (HAS), an enzyme that catalyzes the formation of the extracellular matrix glycosaminoglycan, hyaluronan, within VSMCs. M(Hb) supernatants enhanced HAS production in VSMCs, while knocking down HAS attenuated its anticalcific effect. NF-κB blockade in ApoE-/- mice reduced hyaluronan and increased VC. In human arteries, hyaluronan and HAS were increased in areas of CD163+ macrophage presence. Our findings highlight an important mechanism by which CD163+ macrophages inhibit VC through NF-κB-induced HAS augmentation and thus promote the high-risk plaque development.

Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals.

Importance: Unexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined. Objective: To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes. Design, Setting, and Participants: This genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021. Main Outcomes and Measures: The frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD. Results: The median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants. Conclusions and Relevance: In this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.

Functional and Taxonomic Dysbiosis of the Gut, Urine, and Semen Microbiomes in Male Infertility.

BACKGROUND: Little is known about the role of the genitourinary and gastrointestinal microbiota in the pathogenesis of male infertility. OBJECTIVE: To compare the taxonomic and functional profiles of the gut, semen, and urine microbiomes of infertile and fertile men. DESIGN, SETTING, AND PARTICIPANTS: We prospectively enrolled 25 men with primary idiopathic infertility and 12 healthy men with proven paternity, and we collected rectal swabs, semen samples, midstream urine specimens, and experimental controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed comprehensive semen analysis, 16S rRNA sequencing for quantitative high-resolution taxonomy, and shotgun metagenomics with a median of 140 million reads per sample for functional metabolic pathway profiling. RESULTS AND LIMITATIONS: We identified a diverse semen microbiome with modest similarity to the urinary microbiome. Infertile men harbored increased seminal α-diversity and distinct ß-diversity, increased seminal Aerococcus, and decreased rectal Anaerococcus. Prevotella abundance was inversely associated with sperm concentration, and Pseudomonas was directly associated with total motile sperm count. Vasectomy appeared to alter the seminal microbiome, suggesting a testicular or epididymal contribution. Anaerobes were highly over-represented in the semen of infertile men with a varicocele, but oxidative stress and leukocytospermia were associated with only subtle differences. Metagenomics data identified significant alterations in the S-adenosyl-L-methionine cycle, which may play a multifaceted role in the pathogenesis of infertility via DNA methylation, oxidative stress, and/or polyamine synthesis. CONCLUSIONS: This pilot study represents the first comprehensive investigation into the microbiome in male infertility. These findings provide the foundation for future investigations to explore causality and identify novel microbiome-based diagnostics and therapeutics for men with this complex and emotionally devastating disease. PATIENT SUMMARY: We explored the resident populations of bacteria living in the gut, semen, and urine of infertile and fertile men. We found several important bacterial and metabolic pathway differences with the potential to aid in diagnosing and treating male infertility in the future.

Microscopic spermatic cord denervation for chronic orchialgia/chronic scrotal content pain: operative outcomes and predictors of failure.

BACKGROUND: To describe our institutional outcomes with microscopic spermatic cord denervation (MSCD) for chronic scrotal content paint (CSCP) and identify predictors of treatment failure. METHODS: Retrospective chart review was performed to identify all MSCD performed by two surgeons at a single institution from 2010-2019. Patient demographic data and operative outcomes were collected. Patients were excluded from analysis if no post-operative follow up was available. Success was defined as complete resolution of bothersome pain. Multivariable logistic regression was utilized to identify predictors of treatment failure. RESULTS: During the study period, 101 patients were identified in which 113 MSCD procedures were performed. Final analysis included 103 procedures across 93 patients. Mean age was 41.8 years (SD 13.2), mean BMI was 29.2 kg/m2 (SD 5.96) and median months of pain preceding surgery were 24 (range, 3-300 months). Overall, 75/103 (73%) MSCD were successful. Of the failures, 5 patients had recurrence of pain greater than 6 months after surgery. Only the presence of pelvic floor muscle spasm (PFMS) independently predicted MSCD failure (OR 3.95, P=0.02). 9 of 19 (47%) patients with PFMS experienced treatment failure, while 19 of 84 (23%) without PFMS experienced failure. CONCLUSIONS: MSCD offers a therapeutic option for patients with refractory CSCP. The presence of PFMS is associated with lower surgical success rates. Patients with pre-operatively identified PFMS should be counseled regarding a higher risk of treatment failure.

Assessment of basal implants in compromised ridges.

AIM: The aim of the present study was to evaluate clinically, radiographically, and functionally the outcomes of immediately loaded basal implants when placed in patients with compromised bone/alveolar ridges. MATERIALS AND METHODS: A total of 18 systemically healthy (9 male and 9 female) subjects with compromised bone with poor quantity or quality were included in the study. A total number of 57 implants was placed, out of which 26 implants were placed in maxilla and 31 implants in mandible. There were 6 patients in which single implants were placed and in rest of the 12 patients, multiple implants were placed, out of which full mouth rehabilitation was done in one patient. In 10 patients, implants were placed immediately in fresh extraction socket and in 7 patients, implants were placed in healed edentulous site. In all the patients, loading was done immediately within 72 h of implant placement. All patients were evaluated for primary and secondary stability, pain, periimplant bone levels using IOPA with grid and CBCT, bleeding, suppuration, sulcular bleeding index, prosthetic complications, and patient satisfaction at specified time intervals. RESULT: All the values obtained during the study were expressed in the form of mean, standard deviation, and standard error of the mean. The parameters were compared between groups using Paired t-test for intragroup comparison at a similar time, i.e., baseline, 1 month, and 3 months. The data collected was comprehensively analyzed using SPSS software. All implants were successful, with no incidence of infection, nil mobility at the end of the study period of 6 months. CONCLUSION: Thus, it can be concluded from the present study, that Basal implants can play a vital role in the rehabilitation of patients, where compromised quality and/or quantity of bone is present and additional augmentation procedures would be required for the placement of conventional root form implants.

The conceptual design of 1-ps time resolution neutron detector for fusion reaction history measurement at OMEGA and the National Ignition Facility.

The nuclear burn history provides critical information about the dynamics of the hot-spot formation and high-density fuel-shell assembly of an Inertial Confinement Fusion (ICF) implosion, as well as information on the impact of alpha heating, and a multitude of implosion failure mechanisms. Having this information is critical for assessing the energy-confinement time τE and performance of an implosion. As the confinement time of an ICF implosion is a few tens of picoseconds, less than 10-ps time resolution is required for an accurate measurement of the nuclear burn history. In this study, we propose a novel 1-ps time-resolution detection scheme based on the Pockels effect. In particular, a conceptual design for the experiment on the National Ignition Facility and OMEGA are elaborated upon herein. A small organic Pockels crystal "DAST" is designed to be positioned ∼5 mm from the ICF implosion, which is scanned by a chirped pulse generated by a femto-second laser transmitted through a polarization-maintained optical fiber. The originally linearly polarized laser is changed to an elliptically polarized laser by the Pockels crystal when exposed to neutrons, and the modulation of the polarization will be analyzed. Our study using 35-MeV electrons showed that the system impulse response is 0.6 ps. The response time is orders of magnitude shorter than current systems. Through measurements of the nuclear burn history with unprecedented time resolution, this system will help for a better understanding of the dynamics of the hot-spot formation, high-density fuel-shell assembly, and the physics of thermonuclear burn wave propagation.

Calcium deposition within coronary atherosclerotic lesion: Implications for plaque stability.

Atherosclerotic lesion progression is associated with intimal calcification. The earliest lesion that shows calcification is pathologic intimal thickening in which calcifications appear as microcalcifications that vary in size from <0.5 to 15 µm. The calcifications become larger as plaques progress, becoming punctate (>15 µm to 1 mm in diameter), fragmented (>1 mm), and eventually sheet-like calcification (>3 mm). When stratified by plaque type, maximum calcifications are observed in fibrocalcific plaques, followed by healed plaque ruptures. Lesions of acute thrombi, i.e., plaque rupture and erosions, which are the most frequent causes of acute coronary syndromes, show much less calcification than stable fibrocalcific plaques. Conversely, a calcified nodule, the least common lesion of acute thrombosis, occurs in highly calcified lesions. Pro-inflammatory cytokines observed in unstable plaques may provoke an early phase of osteogenic differentiation of smooth muscle cells (SMCs), a release of calcifying extracellular matrix vesicles, and/or induce apoptosis of macrophages and SMCs, which also calcify. Recent pathologic and imaging based studies indicate that lesions with dense calcifications are more likely to be stable plaques (fibrocalcific plaques), while micro, punctate, or fragmented calcifications are associated with either early stage plaques or unstable lesions (plaque rupture or erosion). Clinical non-invasive computed tomography (CT) studies show that the greater the calcium score, the higher the likelihood of patients developing future acute coronary events. This appears contradictory with the findings from pathologic autopsy studies. However, CT analysis of calcium subtypes is limited by resolution and blooming artifacts. Thus, areas of heavy calcification may not be the cause of future events as pathologic studies suggest. Rather, calcium may be an overall marker for the extent of disease. These types of discrepancies can perhaps be resolved by invasive or non-invasive high resolution imaging studies carried out at intervals in patients who present with acute coronary syndromes versus stable angina patients. Coronary calcium burden is greater in stable plaques than unstable plaques and there is a negative correlation between necrotic core area and area of calcification. Recent clinical studies have demonstrated that statins can reduce plaque burden by demonstrating a reduction in percent and total atheroma volume. However, calcification volume increases. In summary, pathologic studies show that sheet calcification is highly prevalent in stable plaques, while microcalcifications, punctate, and fragmented calcifications are more frequent in unstable lesions. Both pathologic and detailed analysis of imaging studies in living patients can resolve some of the controversies in our understanding of coronary calcification.

Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy.

BACKGROUND: Polycythemia (erythrocytosis) is a known side effect of testosterone (T) replacement therapy (TRT) and appears to correlate with maximum T levels. There is also a well-established association between obstructive sleep apnea (OSA) and the development of polycythemia, which confers additional long-term cardiovascular morbidity. Synergy between TRT and OSA in the development of polycythemia remains poorly understood. AIM: The objective of this study was to retrospectively assess the relationship of OSA and secondary polycythemia in hypogonadal men receiving TRT. METHODS: We performed a retrospective chart review of all men treated by a single provider from 2015 to 2019 for the diagnosis of hypogonadism. Patients who developed a hematocrit of 52% or greater were classified as having polycythemia. OSA was identified via clinical documentation or use of nocturnal continuous positive airway pressure. Demographics, laboratory values, treatment details, and comorbidities were recorded. Data were reported as mean ± SD for parametric variables and median [interquartile range] for non-parametric values. OUTCOME: The primary outcome of this study was the association between OSA and polycythemia in hypogonadal men on TRT. RESULTS: 474 men were included in this study. 62/474 (13.1%) men met the criteria for the diagnosis of polycythemia with a median hematocrit of 53.6 [interquartile range 52.6, 55.5]. Univariate analysis demonstrated a strong positive association between polycythemia and the concomitant diagnosis of OSA in hypogonadal men (P = .002). Even after correcting for age, body mass index (BMI), and peak T levels in the multivariate analysis (P = .01), this relationship remained significant with an odds ratio of 2.09 [95% CI 1.17, 3.76]. 37 men on TRT with polycythemia and OSA were included in the final cohort with a mean age of 59.2 ± 11.4 years, mean BMI of 32.4 ± 6.0, and median time from TRT initiation to polycythemia diagnosis of 3 years. All patients diagnosed with OSA were prescribed continuous positive airway pressure with poor compliance noted in 52.8% of men. 37.8% were managed via phlebotomy and 59.5% were managed via dose de-escalation of TRT. In hypogonadal men on TRT with polycythemia, BMI was the only risk factor strongly associated with OSA (P = .013). CLINICAL TRANSLATION: In hypogonadal men (particularly those with elevated BMI) on TRT who develop secondary polycythemia, a diagnosis of OSA should be strongly considered. STRENGTHS & LIMITATIONS: This is a single provider retrospective study and further studies are needed to assess generalizability. CONCLUSIONS: In this retrospective single-center cohort, the development of polycythemia in hypogonadal men on TRT was associated with an increased prevalence of OSA. Lundy SD, Parekh NV, Shoskes DA. Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy. J Sex Med 2020;17:1297-1303.

Fertility considerations in men with testicular cancer.

The modern approach to cancer management has evolved into a multidisciplinary initiative focused not only on cancer specific and overall survival, but also patient quality of life and survivorship. Future fertility is often a major concern for young patients undergoing cancer therapy. Fertility preservation has emerged as a viable but significantly underutilized option. Patients and families should be aware of the varying effects of antineoplastic therapy on their future fertility to allow for an informed decision regarding their fertility preservation options. In this review we discuss the epidemiology, pathophysiology, and management of fertility in the setting of testicular cancer diagnosis and treatment.

Childless Men at the Time of Vasectomy are Unlikely to Seek Fertility Restoration.

OBJECTIVE: To examine whether men who were childless at the time of vasectomy sought consultation for fertility restoration. METHODS: Retrospective chart review was performed to determine if patients without children at the time of vasectomy sought consultation for fertility restoration (defined as vasectomy reversal or sperm retrieval). If the patient had not been seen in our healthcare system within the previous 12 months, he was contacted by phone to determine whether he had sought consultation for fertility restoration. RESULTS: Of 1656 men, 68 men (4.1%) were childless at the time of vasectomy. Fifteen patients were excluded as they were not followed in our hospital system and were unreachable by phone. Zero patients sought consultation for fertility restoration. CONCLUSION: Our single institution study demonstrated that no men who were childless at the time of vasectomy sought consultation for fertility restoration. Given that there are no other FDA approved methods for nonbarrier sterilization for males, men with no children at the time of vasectomy should receive the same AUA guideline-recommended counseling that men with children receive.

Sox9+ messenger cells orchestrate large-scale skeletal regeneration in the mammalian rib.

Most bones in mammals display a limited capacity for natural large-scale repair. The ribs are a notable exception, yet the source of their remarkable regenerative ability remains unknown. Here, we identify a Sox9-expressing periosteal subpopulation that orchestrates large-scale regeneration of murine rib bones. Deletion of the obligate Hedgehog co-receptor, Smoothened, in Sox9-expressing cells prior to injury results in a near-complete loss of callus formation and rib bone regeneration. In contrast to its role in development, Hedgehog signaling is dispensable for the proliferative expansion of callus cells in response to injury. Instead, Sox9-positive lineage cells require Hh signaling to stimulate neighboring cells to differentiate via an unknown signal into a skeletal cell type with dual chondrocyte/osteoblast properties. This type of callus cell may be critical for bridging large bone injuries. Thus despite contributing to only a subset of callus cells, Sox9-positive progenitors play a major role in orchestrating large-scale bone regeneration. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Prevalence of Spaced and Non-Spaced Dentition and Occlusal Relationship of Primary Dentition and its Relation to Malocclusion in School Children of Davangere.

BACKGROUND: The aim of the current study was carried to determine the relation of spacing, closed dentition, and occlusal relation with malocclusion in the primary dentition in children during deciduous dentition period among school children of Davangere. MATERIALS AND METHODS: A total of 945 school children all having deciduous teeth were included in the study. Informed consent for the child's participation is taken from the school principal. The dentition was examined under natural daylight, and the data was recorded. All the school children were screened for spaced and non-spaced dentition, molar and canine relationship. RESULTS: The results concluded that most of the children showed spaced dentition (82.1%) when compared to non-spaced dentition (17.9%) with males shown more spaced dentition than compared to females. Among all children examined for molar and canine relation, flush terminal molar relation (65%) showed highest among all molar relation followed by mesial step (31%) and distal step (4%), and Class I canine relation (90%) was significant followed by Class II (6%) and Class III canine relation (4%). No significant difference was seen between right and left side. CONCLUSION: The study concludes that determining the malocclusion and its correction at an early age helps in preventing a future complication in permanent dentition since stable primary occlusion leads to ideal occlusion in permanent dentition. Spacing, i.e., primate and physiologic space with the terminal molar relation in primary dentition indicates proper alignment of the permanent dentition.

In vitro Evaluation of Antibacterial Efficacy of Pineapple Extract (Bromelain) on Periodontal Pathogens.

BACKGROUND: Periodontitis is an inflammatory disease resulting in the destruction of periodontal tissues. Various treatment modalities have been tried in the form of mechanical therapy and surgical therapy. Antimicrobial agents have been used as a monotherapy and as an adjunct with mechanical debridement. Various plant extracts have been used as antibacterial agents. Pineapple extract (bromelian) is one such agent. Hence this study was conducted to assess the antibacterial efficacy of bromelain on both aerobic and anaerobic periodontal microorganisms. The aim was to assess the antibacterial efficacy of bromelain on both aerobic and anaerobic periodontal microorganisms. MATERIALS AND METHODS: Minimum inhibitory concentration (MIC) of bromelain was tested on isolated strains of Streptococcus mutans, Enterococcus fecalis Aggregatibacter actinomycetemcomitans (Aa), and Porphyromonas gingivalis (Pg) using serial dilution broth method. RESULTS: S. mutans showed sensitivity at the lowest concentration of 2 mg/ml as compared to E fecalis (31.25 mg/ml) while Pgingivalis showed sensitivity at the lowest concentration of 4.15 mg/ml as compared to Aa (16.6 mg/ml). CONCLUSION: Bromelain exerts an antibacterial effect against potent periodontal pathogens; hence, it may be used as an antibacterial agent. However, further trial has to be conducted to validate this result.

Carotid body tumor as a reversible cause of syncope.

The causes of syncope are diverse and extensive; carotid body tumors are an extremely rare cause of syncope. These rare neoplasms represent less than 0.5% of all head and neck tumors. The authors present a case of a woman with syncope who was found to have a right-sided carotid body tumor. After surgical resection was performed, she did not have any additional syncopal or near-syncopal events. The authors provide a review of the literature on the natural history, presentation, and preferred management of carotid body tumors. With modern diagnostic tools and treatment options, most patients with this diagnosis can expect to recover fully.

Targeted thyroid testing in acute illness: achieving success through audit.

Thyroid tests are done in acutely ill patients who often have confusing transient thyroid abnormalities, despite a lack of clarity about intervention and cost benefit. A retrospective analysis of patients admitted to the Medical Assessment Unit (MAU) was undertaken in 2004 to assess the frequency and utility, pattern of abnormalities and cost of thyroid testing. Guidelines were issued and the audit was repeated in 2008. 53.8% of 1593 subjects were offered thyroid tests in 2004 with a significant reduction to 21.7% of 1176 in 2008 (p<0.001). Free T4 or TSH was outside the reference range in 11.2% (2004) and 7.5% (2008) (p=0.10) and low TSH (52.7% in 2004 and 64.3% in 2008) was commonly combined with normal free T4. Appropriate indications for testing were documented in 43.9 vs 73.7% of patients with abnormal thyroid results (p=0.004) and in 14.3 vs 16% (2004 vs 2008) of a random sample of subjects with normal thyroid results, respectively (p=0.77). Documentation of intervention (25.5. vs 92.9%; p=0.001) and follow-up (45.5 vs 85.7%; p=0.001) had also improved significantly in 2008. We have demonstrated a significant reduction in thyroid testing in acutely ill patients after audit and the issue of guidelines. We currently recommend thyroid tests only in those with previous thyroid disease, the presence of clinical features and risk factors for thyroid disease, the use of relevant drugs, and unexplained tachydysrhythmias. The difficulties in interpreting results, the lack of clarity about intervention and follow up and possible cost savings would argue against an unrestricted policy.

Fluorescence polarization imaging for delineating nonmelanoma skin cancers.

We present a method for detecting nonmelanoma skin cancers using exogenous fluorescence polarization. We built an automated system that permits exogenous fluorescence polarization imaging. It includes a tunable linearly polarized monochromatic light source and a CCD camera equipped with a rotating linear polarizer and a filter to reject excitation light. Two fluorophores that are retained in tumors, toluidine blue and methylene blue, are employed. We demonstrate that fluorescence polarization imaging can be used for accurate delineation of nonmelanoma cancers. The results suggest that this optical technique may be suitable for real-time noninvasive demarcation of epithelial cancers.