Early findings from the NHS Type 2 Diabetes Path to Remission Programme: a prospective evaluation of real-world implementation.

Background: Randomised controlled trials have shown that total diet replacement (TDR) can lead to remission of type 2 diabetes. In 2019, the English National Health Service (NHS) committed to establishing a TDR-based interventional programme delivered at scale within real-world environments; development followed of the NHS Type 2 Diabetes Path to Remission (T2DR) programme, a 12-month behavioural intervention to support weight loss involving an initial 3-month period of TDR. We assessed remission of type 2 diabetes for programme participants.

Who guards the guardian? Mechanisms that restrain APC/C during the cell cycle.

The cell cycle is principally controlled by Cyclin Dependent Kinases (CDKs), whose oscillating activities are determined by binding to Cyclin coactivators. Cyclins exhibit dynamic changes in abundance as cells pass through the cell cycle. The sequential, timed accumulation and degradation of Cyclins, as well as many other proteins, imposes order on the cell cycle and contributes to genome maintenance.

Impact of Detergents on Membrane Protein Complex Isolation.

Detergents play an essential role during the isolation of membrane protein complexes. Inappropriate use of detergents may affect the native fold of the membrane proteins, their binding to antibodies, or their interaction with partner proteins. Here we used cadherin-11 (Cad11) as an example to examine the impact of detergents on membrane protein complex isolation.

The E3 Ubiquitin Ligase SCF(Cyclin F) Transmits AKT Signaling to the Cell-Cycle Machinery.

The oncogenic AKT kinase is a key regulator of apoptosis, cell growth, and cell-cycle progression. Despite its important role in proliferation, it remains largely unknown how AKT is mechanistically linked to the cell cycle. We show here that cyclin F, a substrate receptor F-box protein for the SCF (Skp1/Cul1/F-box) family of E3 ubiquitin ligases, is a bona fide AKT substrate.

VprBP/DCAF1 Regulates the Degradation and Nonproteolytic Activation of the Cell Cycle Transcription Factor FoxM1.

The oncogenic transcription factor FoxM1 plays a vital role in cell cycle progression, is activated in numerous human malignancies, and is linked to chromosome instability. We characterize here a cullin 4-based E3 ubiquitin ligase and its substrate receptor, VprBP/DCAF1 (CRL4), which we show regulate FoxM1 ubiquitylation and degradation. Paradoxically, we also found that the substrate receptor VprBP is a potent FoxM1 activator.

APC/C and SCF(cyclin F) Constitute a Reciprocal Feedback Circuit Controlling S-Phase Entry.

The anaphase promoting complex/cyclosome (APC/C) is an ubiquitin ligase and core component of the cell-cycle oscillator. During G1 phase, APC/C binds to its substrate receptor Cdh1 and APC/C(Cdh1) plays an important role in restricting S-phase entry and maintaining genome integrity. We describe a reciprocal feedback circuit between APC/C and a second ubiquitin ligase, the SCF (Skp1-Cul1-F box).

Measuring wraparound fidelity to make quality improvements.

Wraparound care coordination has offered an individualized family approach to providing services to families in our county for the past decade. Instigated by our county mental health department interested in providing quality improvements to mental health services for families, we assessed the wraparound care coordination process through use of the Wraparound Fidelity Index (WFI), which measures adherence to established principles of wraparound. This article reports on findings from WFI data collected over three summers and reported back to the management team and family organization.

PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signaling.

Biochemical evidence implicates the death-domain (DD) protein PIDD as a molecular switch capable of signaling cell survival or death in response to genotoxic stress. PIDD activity is determined by binding-partner selection at its DD: whereas recruitment of RIP1 triggers prosurvival NF-κB signaling, recruitment of RAIDD activates proapoptotic caspase-2 via PIDDosome formation. However, it remains unclear how interactor selection, and thus fate decision, is regulated at the PIDD platform.

The metabolic syndrome: a modern plague spread by modern technology.

Malnutrition and infectious disease represent the most common health threats facing the developing world. However, increasing technological developments and the expansion of western culture have contributed to the increasing prevalence of the metabolic syndrome. The epidemiologic significance and potential costs to governmental health care systems of an increasing incidence of metabolic syndrome could become high.

Recurrent nocardial brain abscesses treated by repeated stereotactic aspirations.

A case of a 61-year-old diabetic patient who had a new onset simple partial seizure is presented. Past medical history was remarkable for pulmonary sarcoidosis for which the patient was on chronic steroid therapy. Computed tomography scan demonstrated a postcentral abscess which was aspirated under stereotactic guidance.

Adolescent substance use and abuse: recognition and management.

Substance abuse in adolescents is undertreated in the United States. Family physicians are well positioned to recognize substance use in their patients and to take steps to address the issue before use escalates. Comorbid mental disorders among adolescents with substance abuse include depression, anxiety, conduct disorder, and attention-deficit/ hyperactivity disorder.

Shaveless brain surgery: safe, well tolerated, and cost effective.

Neurosurgeons perform operations every day, many of which involve the scalp. There is evidence supporting similar or decreased wound infection rates in the unshaven scalp. Patients with standard scalp incisions were assigned to either shave or shaveless preparations (n = 20).

Seriously emotionally disturbed youth: a needs assessment.

A desire to improve outcomes for children and families led Erie County, New York to collaborate with the University at Buffalo Department of Family Medicine on a needs assessment of children with emotional disturbance. Demographic and behavioral characteristics, as well as service needs were identified through case-based interviews conducted with key informants who provided services to children with emotional disturbance. Family interviews were conducted whenever possible.

Primary care education: measuring instruction to improve quality.

The authors describe a validated instrument to measure instructional quality, using responses from first- and third-year medical students to assess ambulatory training sites.

Social character of materialism.

Scores for 170 undergraduates on Richins and Dawson's Materialism scale were correlated with scores on Kassarjian's Social Preference Scale, designed to measure individuals' character structure. A correlation of .26 between materialism and other-directed social character suggested that an externally oriented reference system guides materialists' perceptions, judgments, acquisitions, and possessions.

Neodymium:YAG laser posterior capsulotomies performed by residents at a Veterans Administration Hospital.

Purpose: To assess the initial efficacy of neodymium:YAG (Nd:YAG) laser posterior capsulotomies performed by residents at a teaching institution and to evaluate the associated complications over an extended follow-up.

Setting: Department of Ophthalmology, Edward Hines, Jr. Veterans Administration Hospital, Hines, Illinois, USA.

Spontaneous involution of a diencephalic astrocytoma.

We present the case of a child with a symptomatic diencephalic astrocytoma which involuted after needle biopsy without any adjuvant therapy. A tendency for certain childhood astrocytomas to regress after partial resection has been previously suggested. However, some authors have doubted whether or not such regression actually occurs.

Malignant non-Hodgkin's lymphoma of the cranial vault: a case report.

We present the case of a 19-year-old patient who was admitted with a subcutaneous scalp lump associated with bilateral papilloedema. CT demonstrated a large heterogeneous vault lesion destroying the right parietal bone. The mass was hyperdense and enhanced slightly with contrast.