Screening and diagnosis of gestational diabetes mellitus

Screening, diagnosis, and treatment of gestational diabetes mellitus (GDM) are common practice, despite controversy regarding benefits. A review of the literature from 1950 to 2006 revealed 3 randomized controlled trials evaluated the treatment of GDM but 2 of these studies lacked power to detect a difference in outcomes. The single trial with sufficient power showed a 67% lower rate of serious perinatal complication (a composite of shoulder dystocia, nerve injury, fracture, and death) and a 53% lower rate of macrosomia with treatment of GDM. There are no well-designed studies evaluating screening or diagnostic strategies. Treatment of GDM may improve some neonatal and obstetric outcomes, but there is limited evidence useful for determining the best screening method or diagnostic test, strategy, and criteria. Ongoing studies may provide some evidence to guide future research and clinical practice.     

Ultrasound-directed transvaginal myolysis: preclinical studies

The ultimate goal is to develop a safe vaginal ultrasound-directed myolysis needle to treat uterine myomas. The specific preclinical study objective was to determine the optimal power to coagulate myomas in hysterectomy specimens with a prototype needle in a prospective preclinical study with an echogenic insulated needle electrode. In phase I of the study, myolysis was performed with ultrasound guidance at various powers and times. In phase II, a 20-W coagulating current was applied at defined distances from the serosa and surface temperatures measured. Myolysis with 10 to 20 W applied 5 to 10 seconds was optimal, because tissue popping occurred at 30 W or more when the needle was 5 mm or less from the serosa. The serosal temperature was never elevated above physiological ranges at any distance at this setting. Ultrasound-directed transvaginal myolysis may provide another option for women with uterine myomas if it is proven safe and effective in future clinical studies. On the basis of the observations in these preclinical studies, myolysis with 20 W for 10 seconds should be a safe parameter for clinical research, because there is no increased serosal temperature at these settings.     

Why has the acceptance of laparoscopic hysterectomy been slow? Results of an anonymous survey of Australian gynecologists

STUDY OBJECTIVE: To determine whether Australian gynecologists would like to increase the proportion of hysterectomies they perform laparoscopically and the factors that might limit their acceptance of laparoscopic hysterectomy (LH). DESIGN: Anonymous postal survey (Canadian Task Force classification III). SETTING: Department of obstetrics and gynecology of a major Australian medical school. PARTICIPANTS: Seven hundred ninety-six certified obstetrician/gynecologists in practice in Australia. MAIN RESULTS: Of 796 respondents, 654 (82%) reported that hysterectomy was part of their normal clinical practice. Of those, 206 (31%) did not perform LH. Respondents who reported performing the highest proportion of LH were those in urban, private hospital settings. Of those who performed hysterectomy, 62% (403/654) reported they did not wish to increase the proportion of LH they undertook. However, of those, 49% (197/403) already performed LH, with 20% (39/197) of that group performing 80% or more of all hysterectomies as LH. Overall, 38% (251/654) of respondents indicated a desire to perform an increased proportion of LH. The commonest factors cited as limited acceptance of LH were insufficient experience and training, lack of hospital equipment, and lack of support from colleagues. CONCLUSION: Many Australian gynecologists report a desire to increase their rate of LH, but those intentions are compromised by problems with training, equipment, and support.     

Transmission of Grapevine Red Blotch Virus by Spissistilus festinus [Say, 1830] (Hemiptera: Membracidae) between Free-Living Vines and Vitis vinifera ‘Cabernet Franc’

Grapevine red blotch disease emerged within the past decade, disrupting North American vine stock production and vineyard profitability. Our understanding of how grapevine red blotch virus (GRBV), the causal agent of the disease, interacts with its Vitis hosts and insect vector, Spissistilus festinus, is limited. Here, we studied the capabilities of S. festinus to transmit GRBV from and to free-living vines, identified as first-generation hybrids of V. californica and V. vinifera ‘Sauvignon blanc’ (Vcal hybrids), and to and from V. vinifera ‘Cabernet franc’ (Vvin Cf) vines. The transmission rate of GRBV was high from infected Vcal hybrid vines to healthy Vcal hybrid vines (77%, 10 of 13) and from infected Vvin Cf vines to healthy Vcal hybrid vines (100%, 3 of 3). In contrast, the transmission rate of GRBV was low from infected Vcal hybrid vines to healthy Vvin Cf vines (15%, 2 of 13), and from infected Vvin Cf vines to healthy Vvin Cf vines (19%, 5 of 27). No association was found between transmission rates and GRBV titer in donor vines used in transmission assays, but the virus titer was higher in the recipient leaves of Vcal hybrid vines compared with recipient leaves of Vvin Cf vines. The transmission of GRBV from infected Vcal hybrid vines was also determined to be trans-stadial. Altogether, our findings revealed that free-living vines can be a source for the GRBV inoculum that is transmissible by S. festinus to other free-living vines and a wine grape cultivar, illustrating the interconnected roles of the two virus hosts in riparian areas and commercial vineyards, respectively, for virus spread. These new insights into red blotch disease epidemiology will inform the implementation of disease management strategies.     

Diplumbane-catalysed solvent- and additive-free hydroboration of ketones and aldehydes

A new diplumbane, namely [Pb(CH₂SiMe₃)₃]₂, was synthesized and structurally characterized. This group 14 element compound was found to catalyse the hydroboration of ketones and aldehydes under mild conditions without the use of additives and solvents, leading to the synthesis of a range of alcohols in high yields after hydrolysis.

A group 14 compound, diplumbane [Pb(CH₂SiMe₃)₃]₂, was synthesized and characterized, and it catalytic application for the efficient hydroboration of ketones and aldehydes was demonstrated for the first time.

The reduction of carbonyl compounds is an important transformation for the synthesis of alcohols, which are ubiquitous in organic chemistry.^1,2 The past decade has witnessed the development of numerous methods for this reaction including catalytic and non-catalytic ones, with particular interest in those involving pinacolborane (HBpin) as a reducing agent.^3,4 Catalytic hydroboration of ketones and aldehydes using HBpin provides a facile approach to various alcohols following easy hydrolysis of the corresponding boronate esters. In addition, this method has advantages such as superior chemoselectivity, low cost, and broad substrate scope over the traditional stoichiometric reduction.⁴ As a result, significant progress has been made with regards to the design and synthesis of effective catalysts for the hydroborative reduction of carbonyl compounds, which has been documented in several recent review articles.^5–8 While early transition metal complexes (containing, for example, Ti,⁹ V,¹⁰ Mn,¹¹ Fe,¹² Co,¹³ Ni,¹⁴ Cu,¹⁵ and Zn¹⁶) have been popular choices of catalysts, attention was expanded to main group element catalysts in recent years. In addition to the highly efficient metal hydridotriphenylborate hydroboration catalysts containing alkali (Li, Na, K) and alkali earth (Mg) metals that were first introduced by Okuda''s group,^17,18 other groups led by Hill,¹⁹ Mulvey,²⁰ and Sen²¹ have developed other useful catalysts with main group metals, including calcium. Moreover, the group 13 element aluminum has been used in organoaluminum hydrides or alkyl complexes for the hydroboration catalysis of ketones and aldehydes by the Roesky,²² Nembenna²³ and our groups,²⁴ respectively. Two examples of gallium-based catalysts were also reported by the Goicoechea²⁵ and Hevia²⁶ groups in 2021. Several catalysts utilizing group 14 elements (mainly Ge and Sn) were reported by the Jones,²⁷ Zhao,²⁸ and Nagendran²⁹ groups, as well as a silane catalyst stabilized by an amidinate ligand, namely PhC(N^tBu)₂SiHCl₂, reported by the Sen group.³⁰ These highlight the potential of main group elements for the development of active hydroboration catalysts.In contrast, the heavier group 14 element, lead, was almost unknown as a hydroboration catalyst. In 2017, Wesemann and co-workers reported a class of Lewis pair complexes, PhCH(PPh₂)M(Ar*) [M = Ge, Sn, or Pb; Ar* = 2,6-(2,4,6-ⁱPr₃C₆H₂)₂C₆H₃], which catalysed the hydroboration of a single aldehyde, hexanal (Scheme 1).³¹ However, no further demonstration of their catalytic activity towards other aldehydes and ketones was reported. Our recent interest in observing active hydroboration catalysts with a broad range of metals across the periodic table has led to the synthesis of an unprecedented diplumbane compound, namely [Pb(CH₂SiMe₃)₃]₂. Herein, we report the X-ray structure of this diplumbane and its application as an effective catalyst for the hydroboration of ketones and aldehydes under additive- and solvent-free conditions.Open in a separate windowScheme 1Lead-catalysed hydroboration of carbonyl compounds.Our recent work has focused on the utilization of 2,2′;6′,2′′-terpyridine (tpy) for the synthesis of novel Co, Mn, V and Al complexes for reduction catalysis.^{10,11a,13a,24} When the reaction of tpy with equimolar PbCl₂ was carried out in a THF solution, an insoluble white solid was obtained, which was isolated and characterized as (tpy)PbCl₂ (see ESI^†). (tpy)PbCl₂ is insoluble in common organic solvents, but well soluble in dimethyl sulfoxide (DMSO). Attempt to crystallizing this complex from a mixture of DMSO/toluene solution was unsuccessful; instead, an inorganic polymer [Pb₂Cl₄(DMSO)₃]_n was isolated without the incorporation of tpy ligand, indicating a M-tpy dissociation has occurred during crystallization, according to X-ray structural analysis (see ESI^†). Solid sample of (tpy)PbCl₂ was further used to react with LiCH₂SiMe₃ (2.2 equiv.) in diethyl ether for 4 h to give a pale-yellow solution after filtration. The concentrated reaction mixture was then cooled to −28 °C, and bright yellow block-like crystals of 1 were obtained in 46% yield (based on Si) after one week. Replacing the tpy ligand with 4′-Cl-tpy for the synthesis led to the isolation of 1 in a similar yield (48%). In addition, two independent attempts to prepare 1 by reacting PbCl₂ with LiCH₂SiMe₃ without the presence of tpy were unsuccessful, leading to unidentified oil. This indicates the significant role played by tpy ligands. It is believed that during the formation of 1, a process involving the oxidation of Pb from Pb^II to Pb^III occurred, along with the possible reduction of tpy ligand. This is consistent with the well-known redox-active nature of tpy.¹⁰ However, attempts to isolating the reduced product of tpy were unsuccessful, probably owing to its poor stability. 1 was characterized by IR, elemental analysis and solution NMR spectroscopy (see ESI^†). The solid-state structure was further revealed by X-ray crystallography. X-ray diffraction analysis confirmed that 1 crystallizes in the trigonal space group P3. The molecular structure of 1 is shown in Scheme 2. The structure features a dinuclear lead hexaalkyl compound, a diplumbane reminiscent of the known compound, [PbMe₂(CH₂SiMe₃)]₂, reported by Pannell in 1994, synthesized from (CH₂SiMe₃)Me₂PbBr and Mg or (Ph₃Sn)Li with yields of 7% and 18%, respectively.³² Our use of tpy as a ligand template using PbCl₂ as a starting material both simplifies the synthesis of this type of diplumbane and improves the yield, introducing a new synthetic methodology for this type of compounds. In 1, both Pb centers adopt a slightly distorted tetrahedral geometry with τ₄ parameters of 0.92 and 0.93, respectively, where a value of 1.00 represents a perfect tetrahedron.³³ The Pb–Pb bond distance is 2.89922(19) Å, slightly shorter than that in [PbMe₂(CH₂SiMe₃)]₂ (2.968(2) Å), yet comparable to those observed in several other R₃Pb–PbR₃ compounds (Pb–Pb bond lengths range from 2.839(2) Å to 2.908(2) Å).³⁴ The Pb–C bond lengths are also close to those reported.³⁴Open in a separate windowScheme 2The X-ray structure of diplumbane 1 with ORTEP diagram drawn at 30% thermal ellipsoids probability level. Selected bond lengths (Å): Pb1–Pb2 = 2.89922(19), Pb1–C11 = 2.260(8), Pb2–C21 = 2.243(8); and angles (°): C11–Pb1–Pb2 = 115.0(2), C11–Pb1–C11A = 103.5(3), C21–Pb2–Pb1 = 114.2(2), C21–Pb2–C21A = 104.4(3).1 was then examined as a catalyst for the hydroboration of ketones. Delightfully, it was found that the reaction of acetophenone with HBpin proceeded well in the presence of 0.25 mol% of 1, and quantitative conversion to the corresponding boronate ester was observed after 16 h under neat conditions at room temperature without the presence of additives. 1-Phenylethanol could be readily isolated in 94% yield after hydrolysis and purification via column chromatography with silica gel (2a, Scheme 3). A gram-scale synthesis of 2a was also carried out to confirm the practical usability of this catalyst. The efficacy of 1 is therefore well comparable to those well-performed transition metal catalysts reported for this reaction.^9–16 In addition, a control experiment using PbCl₂ instead of 1 led to only 5% gas chromatography (GC) yield of the corresponding boronate ester under the same conditions. Next, we applied this method to a broader range of ketones, featuring aromatic, aliphatic and cyclic substrates. The results are illustrated in Scheme 3. Acetophenones bearing halo groups were hydroborated successfully, affording the secondary alcohols 2b and 2c in 90% and 88% isolated yields, respectively. Both electron-donating and -withdrawing groups did not affect the catalytic activity (2d–f). In addition, functionalized ketones such as cyclopropyl phenyl ketone and α,β-unsaturated ketone were reduced selectively on the ketone site to give 2g and 2h with good yields. More challenging diaryl ketones worked as well for the hydroboration catalysed by 1 (2j and 2k). Finally, aliphatic and cyclic ketones were also used as substrates, and similar reactivity was observed (2l–o). However, either 3-acetylpyridine (for 2p) or 2-acetylpyridine was found to be almost inactive for this reaction, likely due to its coordination with 1 leading to deactivation of the reactive intermediate.Open in a separate windowScheme 3Lead-catalysed hydroboration of ketones.^{a a} Conditions: 1 (0.25 mol%), ketone (1.0 mmol) and HBpin (1.1 mmol), neat, 25 °C, 16 h, N₂. Yields of isolated alcohol products after column chromatography. ^b Reaction run at a 10 mmol scale. ^c GC yields of borate esters without hydrolysis using hexamethylbenzene as internal standard.1-Catalysed hydroboration was further extended to various aldehydes, and the results are summarized in Scheme 4. In general, benzaldehydes with halo, electron-donating or -withdrawing groups were hydroborated smoothly by 1 under neat conditions, affording primary alcohols (3a–g) in 84–96% yields. Cinnamaldehyde and aliphatic aldehydes were also active substrates for the hydroboration.Open in a separate windowScheme 4Lead-catalysed hydroboration of aldehydes.^{a a} Conditions: 1 (0.25 mol%), aldehyde (1.0 mmol) and HBpin (1.1 mmol), neat, 25 °C, 16 h, N₂. Yields of isolated alcohol products after column chromatography. ^b GC yields of borate esters without hydrolysis using hexamethylbenzene as internal standard.Next, chemoselective hydroboration was investigated with two reducible groups present. First, intermolecular competition experiments were carried out using benzaldehyde as a substrate in the presence of equimolar acetophenone or methyl benzoate. The results revealed that the aldehyde was selectively converted to the boronate ester, while the ketone and ester remained intact (Scheme 5). Then intramolecular competition reactions were conducted using methyl 4-formylbenzoate or diphenyl chalcone oxide with two reducible functionalities in each molecule. It was observed that the aldehyde or ketone was selectively reduced through hydroboration over the ester or epoxide, and boronate esters 4 and 5 were isolated without hydrolysis in 94% and 84% yields, respectively.Open in a separate windowScheme 5Chemoselective hydroboration catalysed by 1.Since metal hydrides often behave as the active catalyst for transition and main-group metal catalysed hydroboration,^6,35 we propose this as a possible mechanism for 1-catalysed hydroboration. Although attempts at isolating any reactive intermediate and/or a ketone substrate from the reactions of 1 with HBpin were unsuccessful, in situ NMR spectroscopy of the reaction of 1 with HBpin does show the formation of Me₃SiCH₂Bpin, which supports the formation of a possible hydride species I as shown in Scheme 6.³⁶ Thus, we hypothesize that an insertion/σ-bond metathesis type mechanism might have been under operation (Scheme 6). While we propose a mechanism involving a simple lead hydride (I, Scheme 6) generated from the reaction of precatalyst (1) with HBpin, other possible polyhydride species cannot be excluded. Next, C O insertion of carbonyl compound (ketone or aldehyde) into the Pb–H bond would lead to the formation of lead alkoxide IIIvia intermediate II after σ-bond metathesis. The lead alkoxide would then react with HBpin to afford the boronate ester through intermediate IV, releasing the lead hydride I and completing the catalytic cycle.Open in a separate windowScheme 6A plausible mechanism for the hydroboration of carbonyl compounds by 1 as a precatalyst. Only half of the Pb₂ species are shown for intermediates II–IV for clarity.     

Increased amygdala and decreased frontolimbic r esting- s tate functional connectivity in children with aggressive behavior

Childhood maladaptive aggression is associated with disrupted functional connectivity within amygdala-prefrontal circuitry. In this study, neural correlates of childhood aggression were probed using the intrinsic connectivity distribution, a voxel-wise metric of global resting-state brain connectivity. This sample included 38 children with aggressive behavior (26 boys, 12 girls) ages 8–16 years and 21 healthy controls (14 boys, 6 girls) matched for age and IQ. Functional MRI data were acquired during resting state, and differential patterns of intrinsic functional connectivity were tested in a priori regions of interest implicated in the pathophysiology of aggressive behavior. Next, correlational analyses tested for associations between functional connectivity and severity of aggression measured by the Reactive-Proactive Aggression Questionnaire in children with aggression. Children with aggressive behavior showed increased global connectivity in the bilateral amygdala relative to controls. Greater severity of aggressive behavior was associated with decreasing global connectivity in the dorsal anterior cingulate and ventromedial prefrontal cortex. Follow-up seed analysis revealed that aggression was also positively correlated with left amygdala connectivity with the dorsal anterior cingulate, ventromedial and dorsolateral prefrontal cortical regions. These results highlight the potential role of connectivity of the amygdala and medial prefrontal and anterior cingulate cortices in modulating the severity of aggressive behavior in treatment-seeking children.