Development of compounds for targeted degradation of mammalian cryptochrome proteins.

The mammalian cryptochrome proteins (CRY1 and CRY2) are transcriptional repressors most notable for their role in circadian transcriptional feedback. Not all circadian rhythms depend on CRY proteins, however, and the CRY proteins are promiscuous interactors that also regulate many other processes. In cells with chronic CRY deficiency, protein homeostasis is highly perturbed, with a basal increase in cellular stress and activation of key inflammatory signalling pathways.

Chronic CRYPTOCHROME deficiency enhances cell-intrinsic antiviral defences.

The within-host environment changes over circadian time and influences the replication and severity of viruses. Genetic knockout of the circadian transcription factors CRYPTOCHROME 1 and CRYPTOCHROME 2 (/; CKO) leads to altered protein homeostasis and chronic activation of the integrated stress response (ISR). The adaptive ISR signalling pathways help restore cellular homeostasis by downregulating protein synthesis in response to endoplasmic reticulum overloading or viral infections.

Circadian regulation of macromolecular complex turnover and proteome renewal.

Although costly to maintain, protein homeostasis is indispensable for normal cellular function and long-term health. In mammalian cells and tissues, daily variation in global protein synthesis has been observed, but its utility and consequences for proteome integrity are not fully understood. Using several different pulse-labelling strategies, here we gain direct insight into the relationship between protein synthesis and abundance proteome-wide.

Multiple Pathways of LRRK2-G2019S/Rab10 Interaction in Dopaminergic Neurons.

Background: Inherited mutations in the LRRK2 protein are common causes of Parkinson's disease, but the mechanisms by which increased kinase activity of mutant LRRK2 leads to pathological events remain to be determined. In vitro assays (heterologous cell culture, phospho-protein mass spectrometry) suggest that several Rab proteins might be directly phosphorylated by LRRK2-G2019S. An in vivo screen of Rab expression in dopaminergic neurons in young adult Drosophila demonstrated a strong genetic interaction between LRRK2-G2019S and Rab10.

Outcomes of Revisions for Failed Trapeziometacarpal Joint Arthritis Surgery.

Purpose: We compare outcomes of revision surgery for trapeziometacarpal (TM) arthritis with outcomes for both primary and revision surgery for TM arthritis reported in the literature. We hypothesized that patients undergoing revision surgery for TM arthritis would demonstrate pain and functional outcome scores that were worse than those of patients undergoing primary TM surgery.

Methods: A retrospective analysis of all patients undergoing revision TM surgery at a single institution from 1995 to 2015 was performed.

Electronic prescribing system design priorities for antimicrobial stewardship: a cross-sectional survey of 142 UK infection specialists.

Background: The implementation of electronic prescribing and medication administration (EPMA) systems is a priority for hospitals and a potential component of antimicrobial stewardship (AMS).

Objectives: To identify software features within EPMA systems that could potentially facilitate AMS and to survey practising UK infection specialist healthcare professionals in order to assign priority to these software features.

Methods: A questionnaire was developed using nominal group technique and transmitted via email links through professional networks.

Cavity-Enhanced Room-Temperature Broadband Raman Memory.

Broadband quantum memories hold great promise as multiplexing elements in future photonic quantum information protocols. Alkali-vapor Raman memories combine high-bandwidth storage, on-demand readout, and operation at room temperature without collisional fluorescence noise. However, previous implementations have required large control pulse energies and have suffered from four-wave-mixing noise.

Ligamentum flavum hypertrophy in asymptomatic and chronic low back pain subjects.

Purpose: To examine ligamentum flavum thickness using magnetic resonance (MR) images to evaluate its association with low back pain symptoms, age, gender, lumbar level, and disc characteristics.

Materials And Methods: Sixty-three individuals were part of this IRB-approved study: twenty-seven with chronic low back pain, and thirty-six as asymptomatic. All patients underwent MR imaging and computed tomography (CT) of the lumbar spine.

Trends in carpal tunnel surgery: an online survey of members of the American Society for Surgery of the Hand.

Purpose: To investigate the current treatment patterns of carpal tunnel surgery by members of the American Society of Surgeons of the Hand today and to assess how several elements of practice vary by surgeon location and experience.

Methods: An online survey consisting of 10 questions was sent electronically to members of the American Society of Surgeons of the Hand (N = 2,413). A brief description of the study and a link were sent to participants by the investigators.

Reference-frame-independent quantum-key-distribution server with a telecom tether for an on-chip client.

We demonstrate a client-server quantum key distribution (QKD) scheme. Large resources such as laser and detectors are situated at the server side, which is accessible via telecom fiber to a client requiring only an on-chip polarization rotator, which may be integrated into a handheld device. The detrimental effects of unstable fiber birefringence are overcome by employing the reference-frame-independent QKD protocol for polarization qubits in polarization maintaining fiber, where standard QKD protocols fail, as we show for comparison.

Caring for the incarcerated: an orthopedic perspective.

According to the 1976 Supreme Court case of Estelle v Gamble, the government is required to provide prisoners access to the necessary care for known, serious medical needs. Failure to do so violates the Eighth Amendment prohibiting the imposition of "cruel and unusual punishment." Currently, more than 2.

Ruptured abdominal aortic aneurysm presenting as acute unilateral leg swelling--not all swelling below the knee is DVT.

The authors describe a patient with a previously undiagnosed abdominal aortic aneurysm who presented to the emergency department with acute unilateral leg swelling following aneurysm rupture into the vena cava. Abdominal examination raised the suspicion of intra-abdominal pathology which was confirmed with bedside ultrasound, followed by CT aorta. The patient was transferred for urgent repair and made a good recovery.

An alternative method of neck flexion after tracheal resection.

Tracheal resections for benign and malignant disease are well described. The addition of release procedures, including suprathyroid and suprahyoid laryngeal release, has increased the capability of extended tracheal resection and primary reconstruction. Constant neck flexion by a suture between the skin of the point of the chin and midline of the chest over the manubrium is also widely considered paramount to successful tracheal resections.

Delayed closure of persistent postpneumonectomy bronchopleural fistula.

A 73-year-old man with a history of postpneumonectomy empyema and a long-term chest tube since 1979 presented with fever, chills, leukocytosis, and purulent fluid from the left tube thoracostomy. CT scan and bronchoscopy demonstrated a right lower lobe pneumonia and a left mainstem dehiscence with direct communication to the left tube thoracostomy. He underwent primary closure of the bronchopleural fistula with latissimus dorsi muscle flap coverage after antibiotic therapy for right lower lobe pneumonia.

Perioperative factors as predictors of operative mortality and morbidity in pneumonectomy.

Pneumonectomy for lung cancer is associated with significant morbidity and mortality. Risk factors for the morbidity and mortality have been reported, but consistent conclusive data are undetermined. Current accepted 30-day mortality rates for pneumonectomy range from 7 to 11 per cent.

Bridge to recovery for postcardiotomy failure: is there still a role for centrifugal pumps?

Background: Early implantation of centrifugal devices in patients with postcardiotomy cardiogenic shock may provide a bridge to recovery and allow subsequent long-term survival.

Methods: Since January 1989, 62 patients were supported with centrifugal pumps because of failure to wean from cardiopulmonary bypass. Indications were postcardiotomy cardiogenic shock (PCCS) (n = 60), bridge to cardiac retransplantation (n = 1), and right ventricular failure (n = 1).

Evaluation of the potential of transferrin-adriamycin conjugates in the treatment of bladder cancer.

Objective: To assess the ability of a transferrin-adriamycin conjugate (Tf-ADR) to target transferrin receptor (TfR)-positive cancer cells selectively and to overcome drug resistance in bladder cancer cell lines.

Materials And Methods: Two paired sets of cell lines were used: the first was Chinese hamster ovary (CHO) cells (TfR-negative TRVb cells, as a model for normal resting cells, and TRVb-1 cells which were transfected with human TfR), and the second was a pair of bladder cancer cell lines (ADR-sensitive MGH-U1 cells and ADR-resistant MGH-U1R cells). Cell survival curves were determined after treatment with ADR, Tf and Tf-ADR.

A review of intestinal injury from blunt abdominal trauma.

Eighty-five patients who suffered blunt trauma to the small intestine and/or to the colon were treated at either the Royal Brisbane Hospital (RBH), Brisbane, Queensland or the Flinders Medical Centre (FMC), Adelaide, South Australia, between 1980 and 1991. Data were collected by retrospective review of case notes from the medical records departments of both hospitals and analysed with respect to the cause, the anatomical distribution, the diagnostic methods and the mortality of these injuries. There were 129 intestinal injuries (44 colonic and 85 small bowel).

Restrained occupants on the nonstruck side in lateral collisions.

Of injury-producing collisions with high seat belt use, some 25% to 30% are lateral collisions. This paper describes some of the characteristics of those collisions as they relate to the front-seat occupant sitting on the side opposite to the impact. The data came from a stratified sample of in-depth crash investigations conducted in the Birmingham region in the period 1983 to 1989 involving current model cars.