Gallstone Ileus: An Unfortunate Complication after Endoscopic Biliary Drainage

BACKGROUND: Gallstone ileus is a misnomer of intestinal obstruction. This rare entity of gallstone disease happens after episodes of acute cholecystitis, Mirizzi’s syndrome, or even after endoscopic intervention. CASE REPORT: A 17-year-old lady with acute cholecystitis, hepatolithiasis, and choledocholithiasis was endoscopically managed through endoscopic retrograde cholangiopancreatography. She was initially well but complicated with intestinal obstruction the next day. The abdominal radiograph and computed tomography showed a dilated small bowel secondary to gallstone ileus. An emergency laparotomy was performed to relieve the obstruction. CONCLUSION: Gallstone ileus is a rare cause of intestinal obstruction. It must be suspected in a patient with underlying gallstone disease, especially after an endoscopic biliary intervention. Emergency enterotomy and stone extraction are the imperative surgical intervention if the stone is not able to pass out spontaneously

Design, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition

Brequinar, a potent dihydroorotate dehydrogenase (DHODH) inhibitor, has been evaluated in multiple clinical trials as a potential treatment for cancer. To further understand brequinar‐based DHODH inhibition and DHODH′s therapeutic relevance in cancer, we have developed novel brequinar‐based probes. We disclose a 16‐step convergent synthesis of the first brequinar‐PROTAC and a four‐step approach towards the first mitochondrial‐directed brequinar probe. A PROTAC and mitochondria‐directed probe of brequinar both possess cytotoxicity that is superior to brequinar in a colony formation assay.Brequin′ news: A novel convergent synthesis of brequinar‐based probes to induce protein degradation (16 steps) and improve mitochondria accumulation (four steps) is disclosed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138895/1/chem201702999_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138895/2/chem201702999-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138895/3/chem201702999.pd

Recurrent Laryngeal Nerve Injury Secondary to Blunt Trauma; A Rarity

Recurrent laryngeal nerve (RLN) injury is rarely seen following trauma. Trauma can be penetrating or blunt injury. Following the acute event, the most common presentation is hoarseness of voice. Herein we present a case of recurrent laryngeal nerve injury noticed after a blunt trauma. Indirect laryngoscopy helps to identify and diagnose vocal cord palsy while Computed Tomography (CT) scan of neck helps to evaluate the extent of injury as well as to identify the primary cause of the injury. Patient morbidity can be reduced with prompt diagnosis and management

Traumatic blunt injury in polycystic kidney disease: an unfortunate event

Polycystic kidney disease is not a common genetic disorder. Unlike kidneys of a healthy individual, they are well protected by abdominal wall and other visceral organs. Pathological kidneys especially those with organomegaly are predisposed to trauma, even in trivial injury. The management of such cases is still controversial. In this case report, we highlight a middle-aged man who was diagnosed with polycystic kidney disease only after he sustained a blunt kidney injury. His condition was unstable requiring emergency left nephrectomy

High-throughput protein characterization by complementation using DNA barcoded fragment libraries

Our ability to predict, control, or design biological function is fundamentally limited by poorly annotated gene function. This can be particularly challenging in non-model systems. Accordingly, there is motivation for new high-throughput methods for accurate functional annotation. Here, we used complementation of auxotrophs and DNA barcode sequencing (Coaux-Seq) to enable high-throughput characterization of protein function. Fragment libraries from eleven genetically diverse bacteria were tested in twenty different auxotrophic strains of Escherichia coli to identify genes that complement missing biochemical activity. We recovered 41% of expected hits, with effectiveness ranging per source genome, and observed success even with distant E. coli relatives like Bacillus subtilis and Bacteroides thetaiotaomicron. Coaux-Seq provided the first experimental validation for 53 proteins, of which 11 are less than 40% identical to an experimentally characterized protein. Among the unexpected function identified was a sulfate uptake transporter, an O-succinylhomoserine sulfhydrylase for methionine synthesis, and an aminotransferase. We also identified instances of cross-feeding wherein protein overexpression and nearby non-auxotrophic strains enabled growth. Altogether, Coaux-Seq's utility is demonstrated, with future applications in ecology, health, and engineering

Orbital variability of the PSR J2051-0827 Binary System

We have carried out high-precision timing measurements of the binary millisecond pulsar PSR J2051$-$0827 with the Effelsberg 100-m radio telescope of the Max-Planck-Institut f\"ur Radioastronomie and with the Lovell 76-m radio telescope at Jodrell Bank. The 6.5-yrs radio timing measurements have revealed a significant secular variation of the projected semi-major axis of the pulsar at a rate of $\dot x\equiv d(a_{\rm 1} \sin i)/dt = (-0.23\pm 0.03)\times 10^{-12}$, which is probably caused by the Newtonian spin-orbit coupling in this binary system leading to a precession of the orbital plane. The required misalignment of the spin and orbital angular momenta of the companion are evidence for an asymmetric supernova explosion. We have also confirmed that the orbital period is currently decreasing at a rate of $\dot P_{\rm b}=(-15.5 \pm 0.8)\times 10^{-12}$s s$^{-1}$ and have measured second and third orbital period derivatives $d^2P_{\rm b}/dt^2=(+2.1 \pm 0.3)\times 10^{-20} {\rm s^{-1}}$ and $d^3P_{\rm b}/dt^3 =(3.6 \pm 0.6)\times 10^{-28} {\rm s^{-2}}$, which indicate a quasi-cyclic orbital period variation similar to those found in another eclipsing pulsar system, PSR B1957+20. The observed variation of the orbital parameters constrains the maximal value of the companion radius to $R_{\rm c max} \sim 0.06 R_{\odot}$ and implies that the companion is underfilling its Roche lobe by 50 %. The derived variation in the quadrupole moment of the companion is probably caused by tidal dissipation similar to the mechanism proposed for PSR B1957+20. We conclude that the companion is at least partially non-degenerate, convective and magnetically active.Comment: 9 pages, 7 figures; accepted for publication in A&A, minor change

Sex-dependent diversity in ventral tegmental dopaminergic neurons and developmental programing: a molecular, cellular and behavioral analysis

The knowledge that diverse populations of dopaminergic neurons within the ventral tegmental area (VTA) can be distinguished in terms of their molecular, electrophysiological and functional properties, as well as their differential projections to cortical and subcortical regions has significance for key brain functions, such as the regulation of motivation, working memory and sensorimotor control. Almost without exception, this understanding has evolved from landmark studies performed in the male sex. However, converging evidence from both clinical and pre-clinical studies illustrates that the structure and functioning of the VTA dopaminergic systems are intrinsically different in males and females. This may be driven by sex differences in the hormonal environment during adulthood ('activational' effects) and development (perinatal and/or pubertal 'organizational' effects), as well as genetic factors, especially the SRY gene on the Y chromosome in males, which is expressed in a sub-population of adult midbrain dopaminergic neurons. Stress and stress hormones, especially glucocorticoids, are important factors which interact with the VTA dopaminergic systems in order to achieve behavioral adaptation and enable the individual to cope with environmental change. Here, also, there is male/female diversity not only during adulthood, but also in early life when neurobiological programing by stress or glucocorticoid exposure differentially impacts dopaminergic developmental trajectories in male and female brains. This may have enduring consequences for individual resilience or susceptibility to pathophysiological change induced by stressors in later life, with potential translational significance for sex bias commonly found in disorders involving dysfunction of the mesocorticolimbic dopaminergic systems. These findings highlight the urgent need for a better understanding of the sexual dimorphism in the VTA if we are to improve strategies for the prevention and treatment of debilitating conditions which differentially affect men and women in their prevalence and nature, including schizophrenia, attention/deficit hyperactivity disorder, autism spectrum disorders, anxiety, depression and addiction