Exercise-induced increase in muscle insulin sensitivity in men is amplified when assessed using a meal test.

AIMS/HYPOTHESIS: Exercise has a profound effect on insulin sensitivity in skeletal muscle. The euglycaemic-hyperinsulinaemic clamp (EHC) is the gold standard for assessment of insulin sensitivity but it does not reflect the hyperglycaemia that occurs after eating a meal. In previous EHC investigations, it has been shown that the interstitial glucose concentration in muscle is decreased to a larger extent in previously exercised muscle than in rested muscle. This suggests that previously exercised muscle may increase its glucose uptake more than rested muscle if glucose supply is increased by hyperglycaemia. Therefore, we hypothesised that the exercise-induced increase in muscle insulin sensitivity would appear greater after eating a meal than previously observed with the EHC. METHODS: Ten recreationally active men performed dynamic one-legged knee extensor exercise for 1 h. Following this, both femoral veins and one femoral artery were cannulated. Subsequently, 4 h after exercise, a solid meal followed by two liquid meals were ingested over 1 h and glucose uptake in the two legs was measured for 3 h. Muscle biopsies from both legs were obtained before the meal test and 90 min after the meal test was initiated. Data obtained in previous studies using the EHC (n=106 participants from 13 EHC studies) were used for comparison with the meal-test data obtained in this study. RESULTS: Plasma glucose and insulin peaked 45 min after initiation of the meal test. Following the meal test, leg glucose uptake and glucose clearance increased twice as much in the exercised leg than in the rested leg; this difference is twice as big as that observed in previous investigations using EHCs. Glucose uptake in the rested leg plateaued after 15 min, alongside elevated muscle glucose 6-phosphate levels, suggestive of compromised muscle glucose metabolism. In contrast, glucose uptake in the exercised leg plateaued 45 min after initiation of the meal test and there were no signs of compromised glucose metabolism. Phosphorylation of the TBC1 domain family member 4 (TBC1D4; p-TBC1D4Ser704) and glycogen synthase activity were greater in the exercised leg compared with the rested leg. Muscle interstitial glucose concentration increased with ingestion of meals, although it was 16% lower in the exercised leg than in the rested leg. CONCLUSIONS/INTERPRETATION: Hyperglycaemia after meal ingestion results in larger differences in muscle glucose uptake between rested and exercised muscle than previously observed during EHCs. These findings indicate that the ability of exercise to increase insulin-stimulated muscle glucose uptake is even greater when evaluated with a meal test than has previously been shown with EHCs.

GDF15 increases insulin action in the liver and adipose tissue via a ß-adrenergic receptor-mediated mechanism.

Growth differentiation factor 15 (GDF15) induces weight loss and increases insulin action in obese rodents. Whether and how GDF15 improves insulin action without weight loss is unknown. Obese rats were treated with GDF15 and displayed increased insulin tolerance 5 h later. Lean and obese female and male mice were treated with GDF15 on days 1, 3, and 5 without weight loss and displayed increased insulin sensitivity during a euglycemic hyperinsulinemic clamp on day 6 due to enhanced suppression of endogenous glucose production and increased glucose uptake in WAT and BAT. GDF15 also reduced glucagon levels during clamp independently of the GFRAL receptor. The insulin-sensitizing effect of GDF15 was completely abrogated in GFRAL KO mice and also by treatment with the ß-adrenergic antagonist propranolol and in ß1,ß2-adrenergic receptor KO mice. GDF15 activation of the GFRAL receptor increases ß-adrenergic signaling, in turn, improving insulin action in the liver and white and brown adipose tissue.

Sublobar Pulmonary Resection in Children With Congenital Lung Abnormalities: A Systematic Review.

BACKGROUND: Lobectomy is currently the advised resection for symptomatic congenital lung abnormalities (CLA). Sublobar surgery is suggested as an alternative that enables to conserve healthy lung parenchyma. This systematic review aims to explore the outcomes of sublobar surgery in CLA patients as well as the corresponding surgical terminology and techniques. METHODS: A systematic literature search was performed in adherence to PRISMA-P guidelines. The target population consists of children undergoing sublobar pulmonary resection for CLA. All studies were independently assessed by two reviewers, and evaluated by a third reviewer in case of disagreement. RESULTS: The literature search yielded 901 studies of which 18 studies were included, comprising 1167 cases. The median chest tube insertion duration was 3.6 days (range 2.0-6.9 days), the median hospital admission was 4.9 days (range 2.0-14.5 days), and residual disease was diagnosed in 2% - leading to re-operation in 70%. The median incidence of postoperative complications was 15% (range 0-67%). Follow-up imaging was standard-of-care in 2/3 of studies. Due to the absence of standardised terminology, operative details and specification of resection type did not typically relate between studies. CONCLUSIONS: Sublobar resection of CLA lesions could be a viable alternative to lobectomy in certain cases, with the advantage of conserving healthy lung parenchyma. Peri- and postoperative complications are comparable with those reported for conventional lobectomy. The incidence of residual disease following sublobar surgery appears to be lower than commonly stated. To improve comparability between studies, we recommend reporting perioperative characteristics in a structured format. LEVEL OF EVIDENCE: Level IV.

Long-term neurodevelopment in children with resected congenital lung abnormalities.

To determine whether children who underwent resection of a congenital lung abnormality (CLA) are at higher risk for neurodevelopmental impairments than peers in the general population. The study population consisted of children born between 1999-2018 who underwent resection of a symptomatic CLA. Neurocognitive development (intelligence, memory, attention, visuospatial processing, executive functioning) and motor function of this population are monitored through our structured, prospective longitudinal follow-up program at the ages of 30 months, 5, 8, and 12 years. We compared study population scores with Dutch norm values using one-sample t-tests and one-sample binominal proportion tests. Forty-seven children were analyzed. The 8-year-olds showed significant impairments in sustained attention through the Dot Cancellation Test (mean z-scores -2.4; [-4.1; -0.8], p = 0.006 and -7.1; [-12.8; -1.4], p = 0.02 for execution speed and fluctuations respectively). Visuospatial memory was impaired at 8 years, though only in 1 out of 3 assessment tools (Rey Complex Figure Test z-scores (-1.0; [-1.5; -0.5], p < 0.001). Further neurocognitive outcomes were unimpaired at all tested ages. Regarding motor function outcomes, mean z-scores of total motor functioning were unimpaired across assessed ages. However, at 8 years, significantly more children than expected had definite motor problems (18% vs 5%, 95% CI [0.052; 0.403], p = 0.022).   Conclusion: This evaluation reveals impairment in some subtests of sustained attention, visuospatial memory and motor development. However, globally, normal neurodevelopmental outcomes were found throughout childhood. We recommend testing for neurodevelopmental impairments in children who underwent surgery for CLA only if associated morbidities are present or if caregivers express doubts about their daily functioning. What is Known: • In general, surgically managed CLA cases seldom suffer from long-term surgery-related morbidity and show favorable lung function. What is New: • Long-term neurocognitive and motor function outcome appear unimpaired within surgically managed CLA cases. We recommend testing for neurodevelopmental impairments in children who underwent surgery for CLA only if associated morbidities are present or if caregivers express doubts about their daily functioning.

COllaborative Neonatal Network for the first European CPAM Trial (CONNECT): a study protocol for a randomised controlled trial.

INTRODUCTION: Consensus is lacking on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM). For future studies, the CONNECT consortium (the COllaborative Neonatal Network for the first European CPAM Trial)-an international collaboration of specialised caregivers-has established consensus on a core outcome set of outcome parameters concerning respiratory insufficiency, surgical complications, mass effect and multifocal disease. These outcome parameters have been incorporated in the CONNECT trial, a randomised controlled trial which, in order to develop evidence-based practice, aims to compare conservative and surgical management of patients with an asymptomatic CPAM. METHODS AND ANALYSIS: Children are eligible for inclusion after the CPAM diagnosis has been confirmed on postnatal chest CT scan and they remain asymptomatic. On inclusion, children are randomised to receive either conservative or surgical management. Subsequently, children in both groups are enrolled into a standardised, 5-year follow-up programme with three visits, including a repeat chest CT scan at 2.5 years and a standardised exercise tolerance test at 5 years.The primary outcome is exercise tolerance at age 5 years, measured according to the Bruce treadmill protocol. Secondary outcome measures are molecular genetic diagnostics, validated questionnaires-on parental anxiety, quality of life and healthcare consumption-, repeated imaging and pulmonary morbidity during follow-up, as well as surgical complications and histopathology. This trial aims to end the continuous debate surrounding the optimal management of asymptomatic CPAM. ETHICS AND DISSEMINATION: This study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Centre Rotterdam, The Netherlands, has approved this protocol (MEC-2022-0441). Results will be disseminated through peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05701514.

Congenital lung abnormalities on magnetic resonance imaging: the CLAM study.

OBJECTIVES: Follow-up of congenital lung abnormalities (CLA) is currently done with chest computer tomography (CT). Major disadvantages of CT are exposure to ionizing radiation and need for contrast enhancement to visualise vascularisation. Chest magnetic resonance imaging (MRI) could be a safe alternative to image CLA without using contrast agents. The objective of this cohort study was to develop a non-contrast MRI protocol for the follow-up of paediatric CLA patients, and to compare findings on MRI to postnatal CT in school age CLA patients. METHODS: Twenty-one CLA patients, 4 after surgical resection and 17 unoperated (mean age 12.8 (range 9.4-15.9) years), underwent spirometry and chest MRI. MRI was compared to postnatal CT on appearance and size of the lesion, and lesion associated abnormalities, such as hyperinflation and atelectasis. RESULTS: By comparing school-age chest MRI to postnatal CT, radiological appearance and diagnostic interpretation of the type of lesion changed in 7 (41%) of the 17 unoperated patients. In unoperated patients, the relative size of the lesion in relation to the total lung volume remained stable (0.9% (range - 6.2 to + 6.7%), p = 0.3) and the relative size of lesion-associated parenchymal abnormalities decreased (- 2.2% (range - 0.8 to + 2.8%), p = 0.005). CONCLUSION: Non-contrast-enhanced chest MRI was able to identify all CLA-related lung abnormalities. Changes in radiological appearance between MRI and CT were related to CLA changes, patients' growth, and differences between imaging modalities. Further validation is needed for MRI to be introduced as a safe imaging method for the follow-up of paediatric CLA patients. KEY POINTS: • Non-contrast-enhanced chest MRI is able to identify anatomical lung changes related to congenital lung abnormalities, including vascularisation. • At long-term follow-up, the average size of congenital lung abnormalities in relation to normal lung volume remains stable. • At long-term follow-up, the average size of congenital lung abnormalities associated parenchymal abnormalities such as atelectasis in relation to normal lung volume decreases.

The Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey.

Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.

Pre-endoscopy SARS-CoV-2 testing strategy during COVID-19 pandemic: the care must go on.

BACKGROUND: In response to the COVID-19 pandemic, endoscopic societies initially recommended reduction of endoscopic procedures. In particular non-urgent endoscopies should be postponed. However, this might lead to unnecessary delay in diagnosing gastrointestinal conditions. METHODS: Retrospectively we analysed the gastrointestinal endoscopies performed at the Central Endoscopy Unit of Saarland University Medical Center during seven weeks from 23 March to 10 May 2020 and present our real-world single-centre experience with an individualized rtPCR-based pre-endoscopy SARS-CoV-2 testing strategy. We also present our experience with this strategy in 2021. RESULTS: Altogether 359 gastrointestinal endoscopies were performed in the initial period. The testing strategy enabled us to conservatively handle endoscopy programme reduction (44% reduction as compared 2019) during the first wave of the COVID-19 pandemic. The results of COVID-19 rtPCR from nasopharyngeal swabs were available in 89% of patients prior to endoscopies. Apart from six patients with known COVID-19, all other tested patients were negative. The frequencies of endoscopic therapies and clinically significant findings did not differ between patients with or without SARS-CoV-2 tests. In 2021 we were able to unrestrictedly perform all requested endoscopic procedures (> 5000 procedures) by applying the rtPCR-based pre-endoscopy SARS-CoV-2 testing strategy, regardless of next waves of COVID-19. Only two out-patients (1893 out-patient procedures) were tested positive in the year 2021. CONCLUSION: A structured pre-endoscopy SARS-CoV-2 testing strategy is feasible in the clinical routine of an endoscopy unit. rtPCR-based pre-endoscopy SARS-CoV-2 testing safely allowed unrestricted continuation of endoscopic procedures even in the presence of high incidence rates of COVID-19. Given the low frequency of positive tests, the absolute effect of pre-endoscopy testing on viral transmission may be low when FFP-2 masks are regularly used.

Preoperative visualization of congenital lung abnormalities: hybridizing artificial intelligence and virtual reality.

OBJECTIVES: When surgical resection is indicated for a congenital lung abnormality (CLA), lobectomy is often preferred over segmentectomy, mostly because the latter is associated with more residual disease. Presumably, this occurs in children because sublobar surgery often does not adhere to anatomical borders (wedge resection instead of segmentectomy), thus increasing the risk of residual disease. This study investigated the feasibility of identifying eligible cases for anatomical segmentectomy by combining virtual reality (VR) and artificial intelligence (AI). METHODS: Semi-automated segmentation of bronchovascular structures and lesions were visualized with VR and AI technology. Two specialists independently evaluated via a questionnaire the informative value of regular computed tomography versus three-dimensional (3D) VR images. RESULTS: Five asymptomatic, non-operated cases were selected. Bronchovascular segmentation, volume calculation and image visualization in the VR environment were successful in all cases. Based on the computed tomography images, assignment of the CLA lesion to specific lung segments matched between the consulted specialists in only 1 out of the cases. Based on the three 3D VR images, however, the localization matched in 3 of the 5 cases. If the patients would have been operated, adding the 3D VR tool to the preoperative workup would have resulted in changing the surgical strategy (i.e. lobectomy versus segmentectomy) in 4 cases. CONCLUSIONS: This study demonstrated the technical feasibility of a hybridized AI-VR visualization of segment-level lung anatomy in patients with CLA. Further exploration of the value of 3D VR in identifying eligible cases for anatomical segmentectomy is therefore warranted.

Surgery in Neonatal and Pediatric ECMO Patients Other Than Congenital Diaphragmatic Hernia Repair: A 10-Year Experience.

Aim of Study: The use of extracorporeal membrane oxygenation (ECMO) has increased as a result of technological developments and the expansion of indications. Relatedly, the number of patients undergoing surgery during ECMO is also rising, at least in the adult population. Little is known on surgery in children during ECMO-therapy. We therefore aimed to assess the frequencies and types of surgical interventions in neonatal and pediatric patients on ECMO and to analyze surgery-related morbidity and mortality. Methods: We retrospectively collected information of all patients on ECMO over a 10-year period in a single tertiary and designated ECMO-center, excluding patients undergoing cardiac surgery, and correction of congenital diaphragmatic hernia. Chi-squared test and Mann-Whitney U test were used to analyze data. Main Results: Thirty-two of 221 patients (14%) required surgery when on ECMO. Common interventions were thoracotomy (32%), laparotomy (23%), fasciotomy (17%), and surgical revision of ECMO (15%). Complications occurred in 28 cases (88%), resulting in a 50% in-hospital mortality rate. Surgical patients had a longer ICU stay and longer total hospital stay compared to those not receiving surgery during ECMO. No significant difference in mortality was found when comparing surgical to non-surgical patients (50 vs. 41%). Conclusions: Approximately one in seven neonatal or pediatric patients required surgical intervention during ECMO, of whom almost 90% developed a complication, resulting in a 50% mortality rate. These results should be taken into account in counseling.

Myeloma-Modified Adipocytes Exhibit Metabolic Dysfunction and a Senescence-Associated Secretory Phenotype.

Bone marrow adipocytes (BMAd) have recently been implicated in accelerating bone metastatic cancers, such as acute myelogenous leukemia and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity, two key risk factors in multiple myeloma disease prevalence, suggesting that BMAds may influence and be influenced by myeloma cells in the marrow. Here, we provide evidence that reciprocal interactions and cross-regulation of myeloma cells and BMAds play a role in multiple myeloma pathogenesis and treatment response. Bone marrow biopsies from patients with multiple myeloma revealed significant loss of BMAT with myeloma cell infiltration of the marrow, whereas BMAT was restored after treatment for multiple myeloma. Myeloma cells reduced BMAT in different preclinical murine models of multiple myeloma and in vitro using myeloma cell-adipocyte cocultures. In addition, multiple myeloma cells altered adipocyte gene expression and cytokine secretory profiles, which were also associated with bioenergetic changes and induction of a senescent-like phenotype. In vivo, senescence markers were also increased in the bone marrow of tumor-burdened mice. BMAds, in turn, provided resistance to dexamethasone-induced cell-cycle arrest and apoptosis, illuminating a new possible driver of myeloma cell evolution in a drug-resistant clone. Our findings reveal that bidirectional interactions between BMAds and myeloma cells have significant implications for the pathogenesis and treatment of multiple myeloma. Targeting senescence in the BMAd or other bone marrow cells may represent a novel therapeutic approach for treatment of multiple myeloma. SIGNIFICANCE: This study changes the foundational understanding of how cancer cells hijack the bone marrow microenvironment and demonstrates that tumor cells induce senescence and metabolic changes in adipocytes, potentially driving new therapeutic directions.

Synthetic investigations of low-coordinate (N-phosphino-amidinate) nickel chemistry: agostic alkyl complexes and benzene insertion into Ni-H.

Treatment of (PN)NiX (X = NHdipp or OtBu; PN = N-phosphinoamidinate ligand) with Me2PhSiH in benzene solvent afforded the crystallographically characterized, antifacial-coordinated, dinuclear species 1, the formation of which corresponds to the hitherto unknown net Ni-H addition of two equivalents of the putative (PN)NiH intermediate across C[double bond, length as m-dash]C units within a single benzene molecule. Computational analysis supports the view of 1 as being comprised of two cationic (PN)NiII fragments ligated by a substituted butadiene dianion µ2-η3:η3-C6H82- bridging group. Also described is the formation and characterization of three-coordinate (PN)Ni(alkyl) complexes stabilized by ß-agostic (alkyl = Et, 2; n-Bu, 3; n-hexyl, 4) or γ-agostic (alkyl = neopentyl, 5) interactions, and our efforts to employ 2 and 3 as synthons for the generation of (PN)NiHvia ß-hydride elimination. Notably, compound 5 represents both the first crystallographically characterized three-coordinate Ni-alkyl complex featuring a heterobidentate ligation, and the first neutral γ-agostic NiII-alkyl complex.

Capillary Refill-The Key to Assessing Dermal Capillary Capacity and Pathology in Optical Coherence Tomography Angiography.

BACKGROUND/OBJECTIVES: Standard optical coherence tomography angiography (OCTA) has been limited to imaging blood vessels actively undergoing perfusion, providing a temporary picture of surface microvasculature. Capillary perfusion in the skin is dynamic and changes in response to the surrounding tissue's respiratory, nutritional, and thermoregulatory needs. Hence, OCTA often represents a given perfusion state without depicting the actual extent of the vascular network. Here we present a method for obtaining a more accurate anatomic representation of the surface capillary network in human skin using OCTA, along with proposing a new parameter, the Relative Capillary Capacity (RCC), a quantifiable proxy for assessing capillary dilation potential and permeability. METHODS: OCTA images were captured at baseline and after compression of the skin. Baseline images display ambient capillary perfusion, while images taken upon capillary refill display the network of existing capillaries at full capacity. An optimization-based automated vessel segmentation method was used to automatically analyze and compare OCTA image sequences obtained from two volunteers. RCC was then compared with visual impressions of capillary viability. RESULTS: Our OCTA imaging sequence provides a method for mapping cutaneous capillary networks independent of ambient perfusion. Differences between baseline and refill images clearly demonstrate the shortcomings of standard OCTA imaging and produce the RCC biometric as a quantifiable proxy for assessing capillary dilation potential and permeability. CONCLUSION: Future dermatological OCTA diagnostic studies should implement the Capillary Refill Methods over standard imaging techniques and further explore the relevance of RCC to differential diagnosis and dermatopathology. Lasers Surg. Med. © The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

A comparative analysis of hydrosilative amide reduction catalyzed by first-row transition metal (Mn, Fe, Co, and Ni) N-phosphinoamidinate complexes.

A comparative study of the performance of (PN)M(N(SiMe3)2) (M = Mn, Fe, Co, and Ni) pre-catalysts supported by N-phosphinoamidinate ligation, as well as M(N(SiMe3)2)n (M = Li, Na, K, Mn, Fe, and Co) pre-catalysts, in the hydrosilative reduction of selected tertiary amide test substrates using PhSiH3 is reported. Encouraged by the performance observed herein for (PN)Ni(N(SiMe3)2) in the reduction of both N,N-dibenzylbenzamide and N,N-diisopropylbenzamide, further competitive testing involving the known complex (PN)Ni(NHdipp) (dipp = 2,6-diisopropylphenyl), as well as the new and crystallographically characterized mononuclear complexes (PN)Ni(OR) (R = 2,6-dimethylphenyl or tBu), revealed (PN)Ni(OtBu) to be particularly effective in such reduction chemistry, including transformations involving the secondary amides N-benzylbenzamide and caprolactam.

How to improve success rates of endoscopic management for buried bumper syndrome.

BACKGROUND: Buried bumper syndrome (BBS) is a rare complication of percutaneous endoscopic gastrostomy. Complete BBS without visible parts of the inner bumper is a challenge for endoscopic treatment. METHODS AND AIMS: Data base analysis of all procedures performed at our tertiary university endoscopy center between 2000 and 2015 was conducted. Our aim was to improve the success rates of endoscopic treatment using a standardized approach and a pull-modification of the papillotome-based extraction technique in a prospective cohort. RESULTS: Retrospectively, 55 patients were identified (37 men; age 54 ± 16 years). The prospective series comprised 11 patients (8 men; age 63 ± 27 years). Patients with partial BBS were effectively treated by endoscopy in both cohorts (24/25 and 4/4 patients, respectively). For complete BBS (Cyrany grade 3), success rates of endoscopic therapy differed significantly between the cohorts (P = 0.017). In the retrospective cohort, only 38% of patients (9/24 patients) were successfully treated. In the prospective cohort, all six patients (deep-type in five cases) were managed without complications. Patients with extra-gastric tubes underwent primary surgery in both cohorts (six and one patients, respectively). CONCLUSION: A structured approach improved success rates of endoscopic treatment. All patients with an internal bumper verified to lie within the gastric wall can be treated by an experienced investigator using a papillotome-based technique.

Foveal light and dark adaptation in patients with glaucoma and healthy subjects: A case-control study.

INTRODUCTION: To determine whether foveal light and dark adaptation are affected in glaucoma. METHODS: Case-control study with 23 glaucoma patients and 51 controls. Light and dark adaptation were measured twice. After 10 minutes pre-adaptation to 0.0032 cd/m2, the background luminance increased stepwise to 320 (5 log unit step) or 10,000 cd/m2 (6.5 log unit step) for 10 minutes, then it decreased back to 0.0032 cd/m2 for 30 minutes. Foveal contrast sensitivity [CS]) as a function of time was determined using a 1.15 degree increment. Time resolution of the experiments was 30 seconds. Multiple linear regression was used to analyse the effect of glaucoma on the CS plateau and adaptation time (time to reach the plateau minus 3 dB); analyses were adjusted for age and gender. RESULTS: After light adaptation to 320 and 10,000 cd/m2, glaucoma patients had a 0.22 (P<0.001) and 0.13 (P = 0.010) log unit lower CS plateau than controls, respectively. After dark adaptation, this difference was 0.21 (P = 0.018) and 0.30 (P<0.001) log unit, respectively. Light adaptation occurred too fast to determine an accurate light adaptation time. Dark adaptation times of glaucoma patients and controls were similar, for both the 5 (7.2 versus 5.5 minutes; P = 0.10) and the 6.5 (18.2 versus 16.6 minutes; P = 0.14) log unit step. CONCLUSION: After a sudden increase or decrease in luminance, the logCS adaptation curves of glaucoma patients are shifted downwards compared to the curves of healthy subjects. Glaucoma patients have a lower CS plateau than healthy subjects, for both light and dark adaptation; dark adaptation times are similar.

Dehydrogenative B-H/C(sp3 )-H Benzylic Borylation within the Coordination Sphere of Platinum(II).

The first examples of stoichiometric dehydrogenative B-H/C(sp3 )-H benzylic borylation reactions, which are of relevance to catalytic methylarene (di)borylation, are reported. These unusual transformations involving a (κ2 -P,N)Pt(η3 -benzyl) complex, and either pinacolborane or catecholborane, proceed cleanly at room temperature. Density functional calculations suggest that borylation occurs via successive σ-bond metathesis steps, whereby a PtII -H intermediate engages in C(sp3 )-H bond activation-induced dehydrogenation.