👤 Cheryl T Dym

Gallbladder torsion is a rare cause of acute gangrenous cholecystitis; its occurrence within an abdominal hernia has not been previously reported. We present such a case occurring within a parastomal hernia and imaged with unenhanced CT. Show less

The purpose of this study is to determine the proficiency of emergency medicine residents in selecting appropriate radiologic examinations for specific clinical scenarios and to ascertain whether their training improves competency in this area over the course of their residency. An online multiple-choice questionnaire was created. It included 10 clinical scenarios excerpted from the American College of Radiology Appropriateness Criteria guidelines and instructed residents to select the most appropriate initial imaging study. A link and invitation to the survey were e-mailed to the residency program directors and coordinators of all American Council for Graduate Medical Education-accredited emergency medicine residency training programs with the request that they be forwarded to their current residents. Responses were graded, with correct answers derived from the American College of Radiology guidelines. Results were stratified by year of emergency medicine training, and an analysis of variance was performed. A total of 583 residents from at least 77 different emergency medicine residency training programs completed the survey. Overall, the average number of questions answered correctly was 7.1 of 10 (SD, 1.2). First-through fourth-year residents averaged 6.9 (SD, 1.3), 7.1 (SD, 1.2), 7.1 (SD, 1.1), and 7.5 (SD, 1.1) correct answers, respectively. Analysis of variance found no significant difference between the scores of the four classes (p = 0.09). Emergency medicine residents do not show significant improvement over the course of their residency in their ability to choose appropriate imaging studies. This finding suggests that there is a role for more-rigorous focused instruction to better familiarize residents with appropriateness guidelines for diagnostic imaging selection. Show less

The optimal strategy for inducing fertility in men with congenital hypogonadotropic hypogonadism (CHH) is equivocal. Albeit a biologically plausible approach, pretreatment with recombinant FSH (rFSH) before GnRH/human chorionic gonadotropin administration has not been sufficiently assessed. The objective of the study was to test this method. This was a randomized, open-label treatment protocol at an academic medical center. GnRH-deficient men (CHH) with prepubertal testes (<4 mL), no cryptorchidism, and no prior gonadotropin therapy were randomly assigned to either 24 months of pulsatile GnRH therapy alone (inducing endogenous LH and FSH release) or 4 months of rFSH pretreatment followed by 24 months of GnRH therapy. Patients underwent serial testicular biopsies, ultrasound assessments of testicular volume, serum hormone measurements, and seminal fluid analyses. rFSH treatment increased inhibin B levels into the normal range (from 29 ± 9 to 107 ± 41 pg/mL, P < .05) and doubled testicular volume (from 1.1 ± 0.2 to 2.2 ± 0.3 mL, P < .005). Histological analysis showed proliferation of both Sertoli cells (SCs) and spermatogonia, a decreased SC to germ cell ratio (from 0.74 to 0.35), and SC cytoskeletal rearrangements. With pulsatile GnRH, the groups had similar hormonal responses and exhibited significant testicular growth. All men receiving rFSH pretreatment developed sperm in their ejaculate (7 of 7 vs 4 of 6 in the GnRH-only group) and showed trends toward higher maximal sperm counts. rFSH pretreatment followed by GnRH is successful in inducing testicular growth and fertility in men with CHH with prepubertal testes. rFSH not only appears to maximize the SC population but also induces morphologic changes, suggesting broader developmental roles. Show less

Studies on spermatogonial stem cells (SSCs) are of unusual significance because they are the unique stem cells that transmit genetic information to subsequent generations and they can acquire pluripotency to become embryonic stem-like cells that have therapeutic applications in human diseases. MicroRNAs (miRNAs) have recently emerged as critical endogenous regulators in mammalian cells. However, the function and mechanisms of individual miRNAs in regulating SSC fate remain unknown. Here, we report for the first time that miRNA-20 and miRNA-106a are preferentially expressed in mouse SSCs. Functional assays in vitro and in vivo using miRNA mimics and inhibitors reveal that miRNA-20 and miRNA-106a are essential for renewal of SSCs. We further demonstrate that these two miRNAs promote renewal at the post-transcriptional level via targeting STAT3 and Ccnd1 and that knockdown of STAT3, Fos, and Ccnd1 results in renewal of SSCs. This study thus provides novel insights into molecular mechanisms regulating renewal and differentiation of SSCs and may have important implications for regulating male reproduction. Show less

Understanding the extent of genomic transcription and its functional relevance is a central goal in genomics research. However, detailed genome-wide investigations of transcriptome complexity in major mammalian organs have been scarce. Here, using extensive RNA-seq data, we show that transcription of the genome is substantially more widespread in the testis than in other organs across representative mammals. Furthermore, we reveal that meiotic spermatocytes and especially postmeiotic round spermatids have remarkably diverse transcriptomes, which explains the high transcriptome complexity of the testis as a whole. The widespread transcriptional activity in spermatocytes and spermatids encompasses protein-coding and long noncoding RNA genes but also poorly conserves intergenic sequences, suggesting that it may not be of immediate functional relevance. Rather, our analyses of genome-wide epigenetic data suggest that this prevalent transcription, which most likely promoted the birth of new genes during evolution, is facilitated by an overall permissive chromatin in these germ cells that results from extensive chromatin remodeling. Show less

Follicular lymphoid hyperplasia of the palate is a benign lymphoproliferative lesion of unknown pathogenesis. It presents usually in female patients as a painless, firm, well-demarcated, usually nonulcerated, slow-growing lesion on the palate that histopathologically may resemble a lymphoma. The authors describe a patient with this condition that was successfully treated with intralesional steroid injections. Previously reported cases were reviewed to assess the results of various treatment modalities and disease-free outcome. A nonsurgical approach to the management of follicular lymphoid hyperplasia may have better patient acceptance and satisfaction without recurrence. Show less

To determine the feasibility of using gadoxetate disodium for MR urography. We retrospectively reviewed 50 consecutive gadoxetate disodium-enhanced abdominal MRI examinations meeting inclusion criteria. For each examination, 30 min postcontrast hepatobiliary phase sequences were reviewed to assess bilateral collecting system segments, including upper pole, interpolar, and lower pole calyces; renal pelvis; and proximal one-third of ureter. Each segment was assessed for degree of opacification (none, <50%, ≥50%, complete) and susceptibility artifact (none, partial thin rim, thick/complete rim, total obscuration). Opacification and susceptibility scores were also calculated for each examination. The 50 reviewed examinations were performed on 46 patients (26 women, 20 men; mean age, 57 years) and included a total of 1000 segments. Of these, 808 (80.8%) were opacified completely, 103 (10.3%) were opacified ≥50%, 39 (3.9%) were opacified <50%, and 50 (5.0%) were not opacified. Of 1000 segments, no susceptibility artifact was present in 822 (82.2%), while a partial thin rim was present in 113 (11.3%), a thick/complete rim in 64 (6.4%) and total obscuration in 1 (0.1%). Gadoxetate disodium contrast produced a high degree of opacification of the proximal urinary collecting system with low incidence of susceptibility artifact; therefore, it is a feasible contrast agent for MR urography. Show less

Diaminopimelate aminotransferase (DAP-AT) is an enzyme in the lysine-biosynthesis pathway. Conversely, ALD1, a close homologue of DAP-AT in plants, uses lysine as a substrate in vitro. Both proteins require pyridoxal-5'-phosphate (PLP) for their activity. The structure of ALD1 from the flowering plant Arabidopsis thaliana (AtALD1) was solved at a resolution of 2.3 Å. Comparison of AtALD1 with the previously solved structure of A. thaliana DAP-AT (AtDAP-AT) revealed similar interactions with PLP despite sequence differences within the PLP-binding site. However, sequence differences between the binding site of AtDAP-AT for malate, a purported mimic of substrate binding, and the corresponding site in AtALD1 led to different interactions. This suggests that either the substrate itself, or the substrate-binding mode, differs in the two proteins, supporting the known in vitro findings. Show less

Disease of the teeth and their support structures is common and frequently seen at imaging of the head and neck. Recognition of dental disease by the interpreting radiologist has the potential to alter the course of patient care, such as when periapical disease is identified as the cause of sinusitis or pericoronitis is identified as the cause of deep neck infection. Furthermore, incidental recognition of carious lesions in both children and adults who are undergoing CT for other reasons may alert the patient and care team of the need for a dental consultation. In fact, most of the images of dental and periodontal conditions that are used in this article were obtained from CT studies that were performed to investigate other problems. Familiarity with the imaging appearance of common dental conditions, such as hyperdontia and hypodontia, tooth trauma, periodontal disease, caries, periapical disease, odontogenic sinusitis, and deep neck infections, allows the radiologist to render a timely, confident, and specific diagnosis of dental abnormalities, even when such findings are unexpected. Show less

Sugar appetite is influenced by unlearned attractions to sweet taste and learned responses to sugars' taste and post-ingestive actions. In rats, sugar-conditioned flavor preferences (CFP) are attenuated by dopamine D1 (SCH23390: SCH), but not by opioid (naltrexone: NTX), receptor antagonism. Sucrose-CFP occurs in BALB/c and SWR inbred mice that differ in their suppressive effects of SCH and NTX on sucrose intake. The present study examined whether SCH and NTX altered expression of previously learned sucrose-CFP and acquisition (learning) of sucrose-CFP in these strains. In Experiment 1, food-restricted mice were trained (10 one-bottle sessions) to drink a more-preferred flavored (e.g., cherry) 16% sucrose solution (CS+/Sucrose) on odd-numbered days, and a less-preferred flavored (e.g., grape) 0.05% saccharin solution (CS-/Saccharin) on even-numbered days. Two-bottle tests with the flavors mixed in 0.2% saccharin occurred 30 min following vehicle (Veh), SCH (50-800 nmol/kg) or NTX (1-5mg/kg) assessing preference expression. CS+ preference expression in BALB/c and SWR mice following Veh were significantly reduced by SCH and NTX. In Experiment 2, separate groups of BALB/c and SWR mice received Veh, SCH (50 nmol/kg) or NTX (1mg/kg) injections 30 min prior to daily one-bottle training sessions with the CS+/Sucrose and CS-/Saccharin solutions assessing preference acquisition. Subsequent two-bottle tests with the CS+ vs. CS- solutions were conducted without injections. CS+/Sucrose training intakes were reduced by SCH in both strains and by NTX in BALB/c mice. In the initial two-bottle test, sucrose-CFP acquisition was significantly reduced in BALB NTX (54%), but not in BALB SCH (77%) groups relative to the BALB Veh group (85%). In contrast, sucrose-CFP acquisition was significantly reduced in SWR SCH (61%), but not in SWR NTX (83%) groups relative to the SWR Veh group (86%). DA D1 and opioid receptor signaling modulate acquisition and/or expression of sucrose-CFP in mice with significant strain differences observed. Show less

During normal development primordial germ cells (PGCs) derived from the epiblast are the precursors of spermatogonia and oogonia. In culture, PGCs can be induced to dedifferentiate to pluripotent embryonic germ (EG) cells in the presence of various growth factors. Several recent studies have now demonstrated that spermatogonial stem cells (SSCs) can also revert back to pluripotency as embryonic stem (ES)-like cells under certain culture conditions. However, the potential dedifferentiation of SSCs into PGCs or the potential generation of oocytes from SSCs has not been demonstrated before. We report that mouse male SSCs can be converted into oocyte-like cells in culture. These SSCs-derived oocytes (SSC-Oocs) were similar in size to normal mouse mature oocytes. They expressed oocyte-specific markers and gave rise to embryos through parthenogenesis. Interestingly, the Y- and X-linked testis-specific genes in these SSC-Oocs were significantly down-regulated or turned off, while oocyte-specific X-linked genes were activated. The gene expression profile appeared to switch to that of the oocyte across the X chromosome. Furthermore, these oocyte-like cells lost paternal imprinting but acquired maternal imprinting. Our data demonstrate that SSCs might maintain the potential to be reprogrammed into oocytes with corresponding epigenetic reversals. This study provides not only further evidence for the remarkable plasticity of SSCs but also a potential system for dissecting molecular and epigenetic regulations in germ cell fate determination and imprinting establishment during gametogenesis. Show less

Computational design is a test of our understanding of enzyme catalysis and a means of engineering novel, tailor-made enzymes. While the de novo computational design of catalytically efficient enzymes remains a challenge, designed enzymes may comprise unique starting points for further optimization by directed evolution. Directed evolution of two computationally designed Kemp eliminases, KE07 and KE70, led to low to moderately efficient enzymes (k(cat)/K(m) values of ≤ 5 10(4) M(-1)s(-1)). Here we describe the optimization of a third design, KE59. Although KE59 was the most catalytically efficient Kemp eliminase from this design series (by k(cat)/K(m), and by catalyzing the elimination of nonactivated benzisoxazoles), its impaired stability prevented its evolutionary optimization. To boost KE59's evolvability, stabilizing consensus mutations were included in the libraries throughout the directed evolution process. The libraries were also screened with less activated substrates. Sixteen rounds of mutation and selection led to > 2,000-fold increase in catalytic efficiency, mainly via higher k(cat) values. The best KE59 variants exhibited k(cat)/K(m) values up to 0.6 10(6) M(-1)s(-1), and k(cat)/k(uncat) values of ≤ 10(7) almost regardless of substrate reactivity. Biochemical, structural, and molecular dynamics (MD) simulation studies provided insights regarding the optimization of KE59. Overall, the directed evolution of three different designed Kemp eliminases, KE07, KE70, and KE59, demonstrates that computational designs are highly evolvable and can be optimized to high catalytic efficiencies. Show less

The practicing oral and maxillofacial surgeon treating patients with oroantral communication (OAC)/oroantral fistulas should be familiar and competent with the various treatment options available. Multiple techniques are available from purely soft tissue flaps, which have proved to be successful over time, to a combination of hard tissue grafts (autologous, alloplastic, or allograft), which can prove to be useful with the increased demand for implant restorations. Although different procedures have proved to be successful, all are premised on the treatment of any underlying sinusitis, which is associated with a higher risk of recurrent OAC. Show less

Evaluation of the paranasal sinuses is often performed in a purely clinical fashion, without the need for imaging. However, in certain instances imaging may be deemed valuable or even necessary in helping to solve a diagnostic dilemma, confirm a suspected diagnosis, evaluate the extent of a known condition, or assess for an underlying cause of the condition. Computed tomography (CT) and magnetic resonance imaging (MRI) can be useful in confirming a suspected diagnosis or providing additional information regarding causes or complications. CT and MRI play complementary roles in evaluating the rare tumors that may involve the paranasal sinuses. Show less

β-Secretase (β-site amyloid precursor protein-cleaving enzyme 1; BACE1) is a transmembrane aspartic protease that cleaves the β-amyloid precursor protein en route to generation of the amyloid β-peptide (Aβ) that is believed to be responsible for the Alzheimer's disease amyloid cascade. It is thus a prime target for the development of inhibitors which may serve as drugs in the treatment and/or prevention of Alzheimer's disease. In the following determination of the crystal structures of both apo and complexed BACE1, structural analysis of all crystal structures of BACE1 deposited in the PDB and molecular dynamics (MD) simulations of monomeric and `dimeric' BACE1 were used to study conformational changes in the active-site region of the enzyme. It was observed that a flap able to cover the active site is the most flexible region, adopting multiple conformational states in the various crystal structures. Both the presence or absence of an inhibitor within the active site and the crystal packing are shown to influence the flap's conformation. An open conformation of the flap is mostly observed in the apo structures, while direct hydrogen-bonding interaction between main-chain atoms of the flap and the inhibitor is a prerequisite for the flap to adopt a closed conformation in the crystal structures of complexes. Thus, a systematic study of the conformational flexibility of the enzyme may not only contribute to structure-based drug design of BACE1 inhibitors and of other targets with flexible conformations, but may also help to better understand the mechanistic events associated with the binding of substrates and inhibitors to the enzyme. Show less

Mammalian spermatogenesis is a process whereby male germ-line stem cells (spermatogonial stem cells) divide and differentiate into sperm. Although a great deal of progress has been made in the isolation and characterization of spermatogonial stem cells (SSCs) in rodents, little is known about human SSCs. We have recently isolated human G protein-coupled receptor 125 (GPR125)-positive spermatogonia and GDNF family receptor alpha 1 (GFRA1)-positive spermatogonia using a 2-step enzymatic digestion and magnetic-activated cell sorting (MACS) from adult human testes. Cell purities of isolated human GPR125- and GFRA1-positive spermatogonia after MACS are greater than 95%, and cell viability is over 96%. The isolated GPR125- and GFRA1-positive spermatogonia coexpress GPR125, integrin, alpha 6 (ITGA6), THY1 (also known as CD90), GFRA1, and ubiquitin carboxyl-terminal esterase L1 (UCHL1), markers for rodent or pig SSCs/progenitors, suggesting that GPR125- and GFRA1-positive spermatogonia are phenotypically the SSCs in human testis. Human GPR125-positive spermatogonia can be cultured for 2 weeks with a remarkable increase in cell number. Immunocytochemistry further reveals that GPR125-positive spermatogonia can be maintained in an undifferentiated state in vitro. Collectively, the methods using enzymatic digestion and MACS can efficiently isolate and purify SSCs from adult human testis with consistent and high quality. The ability of isolating and characterizing human SSCs could provide a population of stem cells with high purity for mechanistic studies on human SSC self-renewal and differentiation as well as potential applications of human SSCs in regenerative medicine. Show less

Mucogingival conditions are deviations from the normal anatomic relationship between the gingival margin and the mucogingival junction. Mucogingival surgery is plastic surgery designed to correct defects in the gingiva surrounding the teeth. Common mucogingival conditions are recession, absence, or reduction of keratinized tissue, and probing depths extending beyond the mucogingival junction. Surgical techniques used to augment cosmetic mucogingival defects include the free gingival autograft, the subepithelial connective tissue graft, rotational flaps, lateral sliding flaps, coronally repositioned flaps, and the use of acellular dermal matrix grafts. Show less

This article reviews and highlights exodontia tips as well as new techniques to make simple and complex exodontia more predictable and efficient with improved patient outcomes. A discussion of a powered periotome that has been developed to aid in the atraumatic extraction of teeth and another new device, the piezosurgery, increasingly used for outpatient oral surgery procedures are included. Physics forceps, a new type of exodontia forceps, is also discussed in this article. Show less

Antibiotic prophylaxis to prevent infective endocarditis has been controversial through the years, with various changes made to recommendations provided to treating physicians and dentists. The dentist must always use his or her best judgment when applying any guideline. However, it is important to remember that the guidelines may be cited in any malpractice litigation as evidence of the standard of care. Early diagnosis with prompt treatment with effective antimicrobial therapy is the best way to lower the mortality and morbidity. When prescribing antibiotics, the clinician must realize that the overprescription of antibiotics has led to resistance to antibiotic regimens and the rise of antibiotic-resistant bacteria. Show less

Before implant placement, adequate bone must be present; this is a fundamental step in treatment planning for implants. Understanding the basics of bone grafting and reconstruction techniques is critical for successful implant placement. Alveolar bone grafting can be very intimidating when first attempted. With careful instruction, education, and practice, grafting can be accomplished by many practitioners. Different methods incorporate similar surgical principles while leading to the development of more advanced grafting techniques. Show less

Current concepts and recommended treatment for temporomandibular disorders (TMDs) and temporomandibular joint pain and dysfunction have evolved over time. This article attempts to distill the current information for this often confusing topic into relevant clinical issues that will allow the general dental practitioner to be better able to diagnose and interpret clinical findings, and institute a therapeutic regimen that will provide needed relief to patients suffering from TMD dysfunction. Current management methods, both surgical and nonsurgical, are reviewed and discussed. Show less

This article is devoted to risk-management strategies regarding oral surgical procedures in the general dental office. Lawsuits are more likely to be filed following poor outcomes related to oral surgical procedures rather than after operative or prosthetic dental procedures. The article is not meant to discourage practitioners from performing oral surgical procedures if they have the experience, training, and appropriate skill set to complete the planned procedure. Rather, it advises clinicians as to the steps one can take to limit the chances of litigation from occurring, and avoid the emotionally and painful time-consuming process associated with a malpractice lawsuit. Show less

Extraction of impacted teeth is one of the most common surgical procedures performed by oral and maxillofacial surgeons. Every surgical procedure results in some degree of postoperative bleeding and inflammation, typically manifesting as pain and edema. Although the complex physiology of the human body is beyond the scope of this article, the educated clinician should have an understanding of the time line associated with these processes so as to determine whether a patient's complaint of postoperative bleeding, pain, or swelling represents a normal response to surgical trauma or an aberrant reaction. Show less

Endogenous tissue inhibitors of metalloproteinases (TIMPs) have key roles in regulating physiological and pathological cellular processes. Imitating the inhibitory molecular mechanisms of TIMPs while increasing selectivity has been a challenging but desired approach for antibody-based therapy. TIMPs use hybrid protein-protein interactions to form an energetic bond with the catalytic metal ion, as well as with enzyme surface residues. We used an innovative immunization strategy that exploits aspects of molecular mimicry to produce inhibitory antibodies that show TIMP-like binding mechanisms toward the activated forms of gelatinases (matrix metalloproteinases 2 and 9). Specifically, we immunized mice with a synthetic molecule that mimics the conserved structure of the metalloenzyme catalytic zinc-histidine complex residing within the enzyme active site. This immunization procedure yielded selective function-blocking monoclonal antibodies directed against the catalytic zinc-protein complex and enzyme surface conformational epitopes of endogenous gelatinases. The therapeutic potential of these antibodies has been demonstrated with relevant mouse models of inflammatory bowel disease. Here we propose a general experimental strategy for generating inhibitory antibodies that effectively target the in vivo activity of dysregulated metalloproteinases by mimicking the mechanism employed by TIMPs. Show less

During sporulation, Bacillus thuringiensis subsp. israelensis produces a mosquito larvicidal protein complex containing several crystalline and cytolytic (Cyt) toxins. Here, the activated monomeric form of Cyt1Aa, the most toxic Cyt family member, was isolated and crystallized, and its structure was determined for the first time at 2.2 Å resolution. Cyt1Aa adopts a typical cytolysin fold containing a β-sheet held by two surrounding α-helical layers. The absence of a β-strand (between residues V26 and I37) in the dimeric structure of Cyt2Aa led us to deduce that this is the only essential segment for dimer formation and that activation of the toxin occurs by proteolytic processing of its N-terminus. Based on the Cyt1Aa structure, we suggest that the toxicity of Cyt1Aa and other nonrelated proteins, all sharing a cytolysin fold, is correlated with their ability to undergo conformational changes that are necessary prior to their membrane insertion and perforation. This fold allows the α-helical layers to swing away, exposing the β-sheet to insert into the membrane. The identification of a putative lipid binding pocket between the β-sheet and the helical layer of Cyt1Aa supports this mechanism. Sequence-based structural analysis of Cyt1Aa revealed that the lack of activity of Cyt1Ca may be related to the latter's inability to undergo this conformational change due to its lack of flexibility. The pattern of the hemolytic activity of Cyt1Aa presented here (resembling that of pore-forming agents), while differing from that imposed by ionic and nonionic detergents, further supports the pore-forming model by which conformational changes occur prior to membrane insertion and perforation. Show less

To perform a systematic review and meta-analysis to quantitatively assess functional magnetic resonance (MR) imaging lateralization of language function in comparison with the Wada test. This study was determined to be exempt from review by the institutional review board. A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A structured Medline search was conducted to identify all studies that compared functional MR imaging with the Wada test for determining hemispheric language dominance prior to brain surgery. Studies meeting predetermined inclusion criteria were selected independently by two radiologists who also assessed their quality using the Quality Assessment of Diagnostic Accuracy Studies tool. Language dominance was classified as typical (left hemispheric language dominance) or atypical (right hemispheric language dominance or bilateral language representation) for each patient. A meta-analysis was then performed by using a bivariate random-effects model to derive estimates of sensitivity and specificity, with Wada as the standard of reference. Subgroup analyses were also performed to compare the different functional MR imaging techniques utilized by the studies. Twenty-three studies, comprising 442 patients, met inclusion criteria. The sensitivity and specificity of functional MR imaging for atypical language dominance (compared with the Wada test) were 83.5% (95% confidence interval: 80.2%, 86.7%) and 88.1% (95% confidence interval: 87.0%, 89.2%), respectively. Functional MR imaging provides an excellent, noninvasive alternative for language lateralization and should be considered for the initial preoperative assessment of hemispheric language dominance. Further research may help determine which functional MR methods are most accurate for specific patient populations. Show less