Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy: A Single-Center Experience.

BACKGROUND: The use of surgery in patients with locally advanced pancreatic cancer (LAPC) following induction chemotherapy is increasing. However, most series do not report on the total cohort of patients undergoing surgical exploration; therefore, this single-center study investigates outcomes among all consecutive patients with LAPC who underwent surgical exploration. METHODS: We conducted a retrospective, single-center analysis including all consecutive patients with LAPC (Dutch Pancreatic Cancer Group criteria) who underwent surgical exploration with curative intent (January 2014-June 2023) after induction therapy. Primary outcomes were resection rate and overall survival (OS) from the time of diagnosis. RESULTS: Overall, 127 patients underwent surgical exploration for LAPC, whereby 100 patients (78.7%) underwent resection and 27 patients (21.3%) underwent a non-therapeutic laparotomy due to the extent of vascular involvement (n = 11, 8.7%) or occult metastases (n = 16, 12.6%). The overall in-hospital/30-day mortality rate was 0.8% and major morbidity was 31.3% (in patients after resection: 1.0% and 33.3%, respectively). The overall 90-day mortality rate was 5.5%, which included 3.1% mortality due to disease progression. Resection was associated with longer median OS {29 months (95% confidence interval [CI] 26-43) vs. 17 months (95% CI 11-26); p < 0.001} compared with patients undergoing non-therapeutic laparotomy, with corresponding 5-year OS rates of 28.4% and 7.7%. In Cox proportional hazard regression analysis, only pancreatic body/tail tumors independently predicted OS (hazard ratio 1.788 [95% CI 1.042-3.068]). CONCLUSION: This single-center series found a resection rate of 78.7% in patients with LAPC selected for surgical exploration, with a low risk of mortality and morbidity in all explored patients and a 5-year OS rate after resection of 28.4%.

FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs.

The Ser/Thr protein phosphatase 2 A (PP2A) regulates the dephosphorylation of many phosphoproteins. Substrate recognition are mediated by B regulatory subunits. Here, we report the identification of a substrate conserved motif [RK]-V-x-x-[VI]-R in FAM122A, an inhibitor of B55α/PP2A. This motif is necessary for FAM122A binding to B55α, and computational structure prediction suggests the motif, which is helical, blocks substrate docking to the same site. In this model, FAM122A also spatially constrains substrate access by occluding the catalytic subunit. Consistently, FAM122A functions as a competitive inhibitor as it prevents substrate binding and dephosphorylation of CDK substrates by B55α/PP2A in cell lysates. FAM122A deficiency in human cell lines reduces the proliferation rate, cell cycle progression, and hinders G1/S and intra-S phase cell cycle checkpoints. FAM122A-KO in HEK293 cells attenuates CHK1 and CHK2 activation in response to replication stress. Overall, these data strongly suggest that FAM122A is a short helical motif (SHeM)-dependent, substrate-competitive inhibitor of B55α/PP2A that suppresses multiple functions of B55α in the DNA damage response and in timely progression through the cell cycle interphase.

Differential item functioning of the revised Multigroup Ethnic Identity Measure (MEIM-R) in racially and income diverse youth with type 1 diabetes.

OBJECTIVE: Racially minoritized youth with T1D are made vulnerable to disproportionately adverse health outcomes compared to White peers due to enduring systems of oppression. Thus, understanding modifiable psychosocial factors associated with diabetes-related outcomes in racially minoritized youth may help to buffer deleterious effects of racism. One factor meriting exploration is racial-ethnic identity. There is currently limited research on measures fit to assess ethnic identity in youth with chronic illnesses. This study's purpose is to examine the factor structure, reliability, and validity of the revised Multigroup Ethnic Identity Measure (MEIM-R) in a racially- and income-diverse sample of youth with T1D across sociodemographic and illness-related proxies for one's positionality in oppressive systems. METHOD: As part of a larger study examining resilience, 142 youth with T1D ages 12-18 (Mage = 14.66, SDage = 1.62, 55.6% Black/African-American, 44.4% White) completed the MEIM-R and various psychosocial measures. HbA1c levels and illness duration were extracted from medical records and caregivers reported income information. Confirmatory factor analyses compared the structural validity of competing MEIM-R models, and uniform and non-uniform differential item functioning (DIF) was explored across sociodemographic and illness-related factors. RESULTS: While a bifactor structure was supported, the MEIM-R was found to exhibit DIF by race and gender on multiple MEIM-R items and did not demonstrate linear bivariate relations with other psychosocial factors. CONCLUSIONS: Since different MEIM-R item response patterns were observed across racial/ethnic and gender groups, caution is warranted in using this measure in racially and gender diverse youth with T1D.

Most elite athletes return to preinjury competitive activity after surgical treatment for medial malleolus stress fractures.

PURPOSE: To provide return-to-performance outcomes after surgical treatment for medial malleolus stress fractures in the elite athlete. Additionally, to describe an individualised surgical approach in the management of medial malleolus stress fractures. METHODS: Five athletes (six ankles) underwent surgical treatment for a medial malleolus stress fracture. The surgical technique was based on the extent of the fracture line in steps with first arthroscopic debridement of bony spurs, microfracturing of the fracture line and screw fixation. Return-to-performance data included time to return to sport-specific training, normal training, first competitive activity, performance and the return-to-performance rate. RESULTS: Patients returned to sport-specific training at a median of 10 weeks. They started normal training at 16 weeks postoperatively and returned to their first competitive activity after 19 weeks. All patients had bony spurs on the distal tibia which were arthroscopically debrided. One patient received arthroscopic debridement of bony spurs alone. Four patients received additional microfracturing of the fracture line and three patients received screw fixation. All patients achieved clinical and radiographic union on follow-up computed tomography scan at 3 months postsurgery. At latest follow-up, no refractures nor hardware complications, nor any other complications were observed. CONCLUSION: Arthroscopic debridement of bony spurs, debridement and microfracturing of the fracture line and screw fixation are all viable surgical tools in the management of medial malleolus stress fractures in elite athletes. The surgical approach containing these options should be tailored to the individual athlete based on the fracture line in the sagittal plane. While most athletes return to full competitive activity in 3-4 months, time to self-reported return to full performance is often much longer. LEVEL OF EVIDENCE: Level IV.

Nationwide Use and Outcome of Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy.

BACKGROUND: Several international high-volume centers have reported good outcomes after resection of locally advanced pancreatic cancer (LAPC) following chemo(radio)therapy, but it is unclear how this translates to nationwide clinical practice and outcome. This study aims to assess the nationwide use and outcome of resection of LAPC following induction chemo(radio)therapy. PATIENTS AND METHODS: A multicenter retrospective study including all patients who underwent resection for LAPC following chemo(radio)therapy in all 16 Dutch pancreatic surgery centers (2014-2020), registered in the mandatory Dutch Pancreatic Cancer Audit. LAPC is defined as arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion. RESULTS: Overall, 142 patients underwent resection for LAPC, of whom 34.5% met the 2022 National Comprehensive Cancer Network criteria. FOLFIRINOX was the most commonly (93.7%) used chemotherapy [median 5 cycles (IQR 4-8)]. Venous and arterial resections were performed in 51.4% and 14.8% of patients. Most resections (73.9%) were performed in high-volume centers (i.e., ≥ 60 pancreatoduodenectomies/year). Overall median volume of LAPC resections/center was 4 (IQR 1-7). In-hospital/30-day major morbidity was 37.3% and 90-day mortality was 4.2%. Median OS from diagnosis was 26 months (95% CI 23-28) and 5-year OS 18%. Surgery in high-volume centers [HR = 0.542 (95% CI 0.318-0.923)], ypN1-2 [HR = 3.141 (95% CI 1.886-5.234)], and major morbidity [HR = 2.031 (95% CI 1.272-3.244)] were associated with OS. CONCLUSIONS: Resection of LAPC following chemo(radio)therapy is infrequently performed in the Netherlands, albeit with acceptable morbidity, mortality, and OS. Given these findings, a structured nationwide approach involving international centers of excellence would be needed to improve selection of patients with LAPC for surgical resection following induction therapy.

Oral Mucosal Lesions - A Study of 369 Cases.

Background: Diagnosing and treating oral cavity lesions is a challenging task for most of the clinicians due to similar symptoms and clinical appearances. Frequently, histopathology and immunohistochemistry aid in making the diagnosis. Objectives: The objectives were to describe the clinical features, and histopathological features and systemic association in patients with oral mucosal lesions (OML). Materials and Methods: A cross-sectional descriptive study was undertaken at a tertiary care centre in patients with OML. A total of 369 cases with OML were included in the study. Results: Males constituted 61.78% of the cases. History of habits such as tobacco, gutka chewing, smoking, and alcohol was given by 32.25%, 29.81%, 26.56%, and 11.38% of cases, respectively. Common symptoms were soreness, burning sensation, oral pain and ulcers. Both oral and cutaneous involvement was seen in 17.89% of cases. Oral lichen planus (oral LP) constituted largest group of patients (21.96%) wherein reticulate type was the most frequent type and buccal mucosa was the commonest site. Oral carcinomas constituted 20.33% of cases followed by infective etiology (11.92%), vesiculobullous group of diseases (10.30%), aphthous stomatitis (8.94%), premalignant lesions (7.05%) such as leukoplakia (3.80%) and submucous fibrosis (2.44%). Histopathology was done in 209 cases. Clinico-histopathological correlation was seen in oral LP (90.27%), oral pemphigus (82.35%), and malignancies (98.66%). Conclusion: Oral LP formed the largest group of cases followed by Oral squamous cell carcinoma (SCC). Several rare conditions, such as Melkersson-Rosenthal syndrome and blue rubber bleb nevus syndrome were also a part of the study. Thorough clinical and histopathological examination in this diverse group of diseases clinches the diagnosis.

FAM122A ensures cell cycle interphase progression and checkpoint control as a SLiM-dependent substrate-competitive inhibitor to the B55⍺/PP2A phosphatase.

The Ser/Thr protein phosphatase 2A (PP2A) is a highly conserved collection of heterotrimeric holoenzymes responsible for the dephosphorylation of many regulated phosphoproteins. Substrate recognition and the integration of regulatory cues are mediated by B regulatory subunits that are complexed to the catalytic subunit (C) by a scaffold protein (A). PP2A/B55 substrate recruitment was thought to be mediated by charge-charge interactions between the surface of B55α and its substrates. Challenging this view, we recently discovered a conserved SLiM [ RK ]- V -x-x-[ VI ]- R in a range of proteins, including substrates such as the retinoblastoma-related protein p107 and TAU (Fowle et al. eLife 2021;10:e63181). Here we report the identification of this SLiM in FAM122A, an inhibitor of B55α/PP2A. This conserved SLiM is necessary for FAM122A binding to B55α in vitro and in cells. Computational structure prediction with AlphaFold2 predicts an interaction consistent with the mutational and biochemical data and supports a mechanism whereby FAM122A uses the 'SLiM' in the form of a short α-helix to dock to the B55α top groove. In this model, FAM122A spatially constrains substrate access by occluding the catalytic subunit with a second α-helix immediately adjacent to helix 1. Consistently, FAM122A functions as a competitive inhibitor as it prevents binding of substrates in in vitro competition assays and the dephosphorylation of CDK substrates by B55α/PP2A in cell lysates. Ablation of FAM122A in human cell lines reduces the rate of proliferation, progression through cell cycle transitions and abrogates G1/S and intra-S phase cell cycle checkpoints. FAM122A-KO in HEK293 cells results in attenuation of CHK1 and CHK2 activation in response to replication stress. Overall, these data strongly suggest that FAM122A is a 'SLiM'-dependent, substrate-competitive inhibitor of B55α/PP2A that suppresses multiple functions of B55α in the DNA damage response and in timely progression through the cell cycle interphase.

PD-1 and PD-L1 Expression in Indian Women with Breast Cancer.

OBJECTIVE: The interaction between programmed cell death protein 1 (PD-1) on activated T-lymphocytes and programmed death-ligand 1 (PD-L1) on tumor cells or antigen-presenting cells sends immunosuppressive signals leading to the escape of tumor cells from the host anti-tumor immune response. Inhibiting this interaction with antibodies against PD-1 or PD-L1 is emerging as a valuable therapeutic strategy. However, tissue distribution patterns for PD-L1 and PD-1 in breast cancer patients from India are not reported, yet many clinical trials are underway. In this study the expression of PD-1 and PD-L1 in breast cancer patient samples from India was characterized. MATERIALS AND METHODS: The study included 392 cases of operated breast cancer (2012-2017) from a tertiary cancer care center in Bangalore, Karnataka, India. Paraffin blocks were retrievable and receptor status was known. Immunohistochemistry (IHC) was performed using anti-PD-L1 and anti-PD-1 antibodies. RNA was isolated from 76 fresh tumors and nine adjacent normal tissues (2019). PD-L1 transcript levels were measured by RT-qPCR using Hypoxanthine-guanine phosphoribosyl transferase (HPRT) as a reference gene. RESULTS: Based on IHC, PD-1 expression within tumor-infiltrating immune cells (TIICs) was observed in 55/385 cases (14%) across all breast cancer types. In triple-negative breast cancer (TNBC), 21/132 cases (16%) showed PD-1 staining in TIICs. The overall expression of PD-L1 in breast tumor cells across all breast cancer subtypes and TIICs was 11% (41/378) and 39% (151/385), respectively. A relatively higher proportion of TNBC cases had PD-L1 expression in tumor cells (17/132 cases, 13%) and immune cells (68/132 cases, 52%). We also detected PD-L1 transcript expression by qRT-PCR in freshly isolated tumor samples. CONCLUSION: These findings show that around 52% (68/132) of the TNBC cases express PD-L1 in TIICs. Hence, anti-PD-1/PD-L1 therapy alone or combined with chemotherapy may be a promising treatment for TNBC in Indian patients.

A meta-analysis of the global impact of the COVID-19 pandemic on stroke care & the Houston Experience.

OBJECTIVE: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston. METHODS: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times. RESULTS: A total of 32,640 stroke admissions from 29 studies were assessed. Compared to prepandemic period, the mean ratio of stroke admissions during the pandemic was 70.78% [95% CI, 65.02%, 76.54%], ICH cases was 83.10% [95% CI, 71.01%, 95.17%], tPA cases was 81.74% [95% CI, 72.33%, 91.16%], and MT cases was 88.63% [95% CI, 74.12%, 103.13%], whereas DTN time was 104.48% [95% CI, 95.52%, 113.44%] and DTG was 104.30% [95% CI, 81.99%, 126.61%]. In Houston, a total of 4808 cases were assessed. There was an initial drop of ~30% in cases at the pandemic onset. Compared to 2019, there was a significant reduction in mild strokes (NIHSS 1-5) [N (%), 891 (43) vs 635 (40), P = 0.02]. There were similar mean (SD) (mins) DTN [44 (17) vs 42 (17), P = 0.14] but significantly prolonged DTG times [94 (15) vs 85 (20), P = 0.005] in 2020. INTERPRETATION: The COVID-19 pandemic led to a global reduction in stroke admissions and treatment interventions and prolonged treatment time metrics.

Referral patterns for catheter-directed thrombolysis for iliofemoral deep venous thrombosis.

OBJECTIVES: Post thrombotic syndrome (PTS) is a serious complication of deep venous thromboses (DVTs). PTS occurs more frequently and severely following iliofemoral DVT compared to distal DVTs. Catheter directed thrombolysis (CDT) of iliofemoral DVTs may reduce PTS incidence and severity.We aimed to determine the rate of iliofemoral DVT within our institution, their subsequent management, and compliance with NICE guidelines. METHODS: Retrospective review of all DVTs diagnosed over a 3-year period was conducted. Cases of iliofemoral DVT were identified using ICD-10 codes from patient notes, and radiology reports of Duplex scans. Further details were retrieved, such as patient demographics and referrals to vascular services. NICE guidance was applied to determine if patients would have been suitable for CDT. A survey was sent to clinicians within medicine to identify awareness of CDT and local guidelines for iliofemoral DVT management. RESULTS: 225 patients with lower limb DVTs were identified. Of these, 96 were radiographically confirmed as iliofemoral DVTs. The median age was 77. 67.7% of iliofemoral DVTs affected the left leg. Right leg DVTs made up 30.2% and 2.1% were bilateral DVTs. Of the 96 iliofemoral DVTs, 21 were deemed eligible for CDT. Only 3 patients (14.3%) were referred to vascular services, and 3 received thrombolysis.From our survey, 95.5% of respondents suggested anticoagulation alone as management for iliofemoral DVT. Only one respondent recommended referral to vascular services. There was a knowledge deficiency regarding venous anatomy, including superficial versus deep veins. CONCLUSIONS: CDT and other mechanochemical procedures have been shown to improve outcomes of patients post-iliofemoral DVT, however a lack of awareness regarding CDT as a management option results in under-referral to vascular services. We suggest closer relations between vascular services and their "tributary" DVT clinics, development of guidelines and robust care pathways in the management of iliofemoral DVT.

The BOAST recommendations for care of the older or frail orthopaedic trauma patient.

Safe and effective care for the elderly or physiologically frail patient in cases of trauma requires a multidisciplinary perioperative approach. This article expands upon the British Orthopaedic Association Standards for Trauma and Orthopaedics guidelines for the management of the older or frail orthopaedic trauma patient. Optimisation of the patient is key to a successful surgical outcome, because these patients often have significant comorbidities involving bone health, nutrition, cognitive function and cardiovascular stability. This article discusses the evidence base for tailoring the management of these patients and the importance of doing so in an ageing population. It considers the requisite preoperative procedures and investigations, guidelines for specific cases such as comatose patients or those with complex fractures, and ceiling of care discussions, and then focuses on the postoperative period, including physiotherapy, rehabilitation goals and medical management.

Biochemical and genetic analyses of N metabolism in maize testcross seedlings: 2. Roots.

KEY MESSAGE: Intracellular factors differentially affected enzyme activities of N assimilation in the roots of maize testcrosses where alanine aminotransferase and glutamate synthase were the main enzymes regulating the levels of glutamate. N is a key macronutrient for plant growth and development. Breeding maize with improved efficiency in N use could help reduce environmental contamination as well as increase profitability for the farmers. Quantitative trait loci (QTL) mapping of traits related to N metabolism in the root tissue was undertaken in a maize testcross mapping population grown in hydroponic cultures. N concentration was negatively correlated with root and total dry mass. Neither the enzyme activities nor metabolites were appreciably correlated between the root and leaf tissues. Repeatability measures for most of the enzymes were lower than for dry mass. Weak negative correlations between most of the enzymes and dry mass resulted likely from dilution and suggested the presence of excess of enzyme activities for maximal biomass production. Glutamate synthase and alanine aminotransferase each explained more variation in glutamate concentration than either aspartate aminotransferase or asparagine synthetase whereas glutamine synthetase was inconsequential. Twenty-six QTL were identified across all traits. QTL models explained 7-43% of the variance with no significant epistasis between the QTL. Thirteen candidate genes were identified underlying QTL within 1-LOD confidence intervals. All the candidate genes were located in trans configuration, unlinked or even on different chromosomes, relative to the known genomic positions of the corresponding structural genes. Our results have implications in improving NUE in maize and other crop plants.

BET proteins in abnormal metabolism, inflammation, and the breast cancer microenvironment.

Obesity and its associated pathology Type 2 diabetes are two chronic metabolic and inflammatory diseases that promote breast cancer progression, metastasis, and poor outcomes. Emerging critical opinion considers unresolved inflammation and abnormal metabolism separately from obesity; settings where they do not co-occur can inform disease mechanism. In breast cancer, the tumor microenvironment is often infiltrated with T effector and T regulatory cells programmed by metabolic signaling. The pathways by which tumor cells evade immune surveillance, immune therapies, and take advantage of antitumor immunity are poorly understood, but likely depend on metabolic inflammation in the microenvironment. Immune functions are abnormal in metabolic disease, and lessons learned from preclinical studies in lean and metabolically normal environments may not translate to patients with obesity and metabolic disease. This problem is made more urgent by the rising incidence of breast cancer among women who are not obese but who have metabolic disease and associated inflammation, a phenotype common in Asia. The somatic BET proteins, comprising BRD2, BRD3, and BRD4, are new critical regulators of metabolism, coactivate transcription of genes that encode proinflammatory cytokines in immune cell subsets infiltrating the microenvironment, and could be important targets in breast cancer immunotherapy. These transcriptional coregulators are well known to regulate tumor cell progression, but only recently identified as critical for metabolism, metastasis, and expression of immune checkpoint molecules. We consider interrelationships among metabolism, inflammation, and breast cancer aggressiveness relevant to the emerging threat of breast cancer among women with metabolic disease, but without obesity.

Factors Influencing the Regional Dynamics of Butternut Canker.

Butternut (Juglans cinerea) is an important component of native biodiversity in eastern North America. Of urgent concern is the survival of butternut, whose populations are declining rapidly, in large part due to an exotic pathogen, Ophiognomonia clavigignenti-juglandacearum, that causes butternut canker. The disease presently occurs throughout the range of butternut in North America, causing branch and stem cankers, dieback, and tree mortality. Despite the existential threat posed by O. clavigignenti-juglandacearum to butternut, a detailed understanding of the factors that drive cross-scale disease patterns is lacking. Therefore, we investigated the association of a range of factors, including tree attributes, topography, and weather, with butternut canker spatial dynamics at different scales using data collected in the province of Quebec, Canada. Trunk canker damage and dieback showed distinct geographic patterns. Bark phenotype was not significantly associated with trunk canker damage. Results suggest that open or dominant trees may show less dieback than intermediate or suppressed trees. Probability of the presence of trunk canker and percent dieback were proportional to the tree diameter at breast height. Temperature was positively associated with disease severity at a 1-km2 scale. Our results provide strong evidence that multiple factors, notably weather, influence butternut canker epidemiology.

Biochemical and genetic analyses of N metabolism in maize testcross seedlings: 1. Leaves.

KEY MESSAGE: Aside from the identification of 32 QTL for N metabolism in the seedling leaves of a maize testcross population, alanine aminotransferase was found to be a central enzyme in N assimilation. Excessive application of nitrogen (N) fertilizer to grow commercial crops like maize is a cause of concern because of the runoff of excess N into streams and rivers. Breeding maize with improved N use efficiency (NUE) would reduce environmental pollution as well as input costs for the farmers. An understanding of the genetics underlying N metabolism is key to breeding for NUE. From a set of 176 testcrosses derived from the maize IBMsyn10 population grown in hydroponics, we analyzed the youngest fully expanded leaf at four-leaf stage for enzymes and metabolites related to N metabolism. Three enzymes, along with one metabolite explained 24% of the variation in shoot dry mass. Alanine aminotransferase (AlaAT) stood out as the key enzyme in maintaining the cellular level of glutamate as it alone explained 58% of the variation in this amino acid. Linkage mapping revealed 32 quantitative trait loci (QTL), all trans to the genomic positions of the structural genes for various enzymes of N assimilation. The QTL models for different traits accounted for 7-31% of the genetic variance, whereas epistasis was generally not significant. Five coding regions underlying 1-LOD QTL confidence intervals were identified for further validation studies. Our results provide evidence for the key role of AlaAT in N assimilation likely through homeostatic control of glutamate levels in the leaf cells. The two QTL identified for this enzyme would help to select desirable recombinants for improved N assimilation.

Data for chitin binding activity of Moringa seed resistant protein (MSRP).

Chitin binding activity of moringa seed resistant protein (MSRP) isolated from defatted moringa seed flour was investigated in the present study "Characterization of soluble dietary fiber from Moringa oleifera seeds and its immunomodulatory effects" (S. Anudeep, V.K. Prasanna, S.M. Adya, C. Radha, 2016) [1]. The assay reaction mixture contained 0.4 mg/ml of MSRP and different amounts (20-100 mg) of chitin. MSRP exhibited binding activity over wide range of chitin concentration. Maximum binding activity was observed at 80 mg of chitin. The property of MSRP to bind chitin can be exploited for its purification.

Oviposition by Female Plodia interpunctella (Lepidoptera: Pyralidae): Description and Time Budget Analysis of Behaviors in Laboratory Studies.

The oviposition behavior of the Indian meal moth, Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae), a major insect pest of durable stored foods, was studied in small experimental arenas under laboratory conditions using videography, and a time budget analysis of its behaviors was documented. Resting gravid females typically became active shortly after the start of the scotophase. The characteristic behaviors exhibited by mated females prior to oviposition included antennal movement, grooming of antennae and mouth parts using the forelegs, walking or flying, and abdomen bending and dragging. Pre-oviposition behaviors such as antennal grooming and walking or flying were observed to alternate several times before females commenced the abdominal dragging behavior that preceded egg laying. Eggs were laid singly or sometimes in groups, either freely or stuck to food material. Gravid females showed little or no movement during the photophase; however, they actively flew and oviposited during the scotophase. Females allocated only a small portion of their time to oviposition while the rest of the time was spent away from food. Females oviposited on food material by making repeated visits, predominantly during the first four hours of the scotophase. Visits and time spent on food declined as the scotophase advanced.

Discovery and Characterization of a Water-Soluble Prodrug of a Dual Inhibitor of Bacterial DNA Gyrase and Topoisomerase IV.

Benzimidazole 1 is the lead compound resulting from an antibacterial program targeting dual inhibitors of bacterial DNA gyrase and topoisomerase IV. With the goal of improving key drug-like properties, namely, the solubility and the formulability of 1, an effort to identify prodrugs was undertaken. This has led to the discovery of a phosphate ester prodrug 2. This prodrug is rapidly cleaved to the parent drug molecule upon both oral and intravenous administration. The prodrug achieved equivalent exposure of 1 compared to dosing the parent in multiple species. The prodrug 2 has improved aqueous solubility, simplifying both intravenous and oral formulation.

In-hospital treatment and outcomes of heart failure in specialist and non-specialist services: a retrospective cohort study in the elderly.

BACKGROUND: Heart failure is common in the elderly and is associated with high rates of hospitalisation, readmission and mortality. International guidelines however are not frequently implemented in this population. METHODS: We retrospectively studied the clinical profile, investigations, treatment on discharge, length of hospital stay, readmission rate and mortality in 261 patients, aged ≥75 years, with a discharge diagnosis of heart failure. Clinical frailty was estimated using the Canadian Study of Health and Aging clinical frailty scale. RESULTS: Hypertension (64%), atrial fibrillation (50.6%) and ischaemic heart disease (46%) were common, and 75.6% of patients were clinically vulnerable or frail. 23.5% of admitters had an inpatient echocardiogram and 20% of patients had at least one readmission episode for heart failure. On discharge, 64.6% of admissions were treated with an ACE inhibitor or angiotensin II receptor antagonist, 49.3% with a ß blocker and 28.7% with an aldosterone receptor antagonist (ARA). Patients discharged from cardiology wards were more likely to receive a ß blocker (p<0.05) versus care of elderly (COE) wards and readmitters were more likely to receive an ARA (p<0.05) versus patients with a single admission. In total, 34 inpatient deaths were recorded (13%) and 80 deaths (30.7%) were recorded long-term (median follow-up 337 days). Long-term mortality was significantly lower in single admitters versus readmitters (p<0.0001) and in those managed on cardiology wards versus COE wards (p<0.05). CONCLUSIONS: Compared with patients hospitalised on geriatric wards, those admitted to cardiology units were discharged more frequently with recommended medications and had a lower long-term mortality.