Role of Mifepristone in Trial of Labour after Previous Caesarean Delivery in Intrauterine Fetal Death.

When a baby dies in utero, the options are either to wait for spontaneous labour or to induce it. An obstetrician, encounters with a perplexity of choosing a management plan when this worst situation of IUFD coalesced by history of previous caesarean delivery. The ideal drug for the termination should not only be efficacious and cost-effective, but also be convenient enough to avoid operative interference arising from a wasted pregnancy. The study was aimed to evaluate efficacy, safety and compliance of oral mifepristone in trial of labour in case of IUFD after previous caesarean section. This was a cross sectional descriptive type of observational study conducted in the Department of Obstetrics and Gynaecology, Mymensingh Medical College Hospital, Bangladesh from February 2018 to August 2018. Total 50 patients were selected purposively based on inclusion criteria and diagnosed as IUFD with previous caesarean delivery. The patients were received mifepristone once and reviewed after 48 hours and those who were not attained favourable Bishop's score were counseled for mechanical induction. Antibiotics and analgesia were administered according to requirement. Data analysis was done using SPSS version 22.0. All the 50 women received 200 mg oral mifepristone. Forty-four 44(88.0%) women was delivered vaginally among them 18(36.0%) were delivered following mifepristone induction only and 26(52.0%) required additional induction method. The earliest induction to delivery interval following mifepristone was 13 hours. Twenty eight (63.6%) cases were discharged within 72-120 hours. After 48 hours following induction there was significant improvement of Bishop's score. In this study 6(12.0%) out of 50 cases were reasoned for laparotomy and blood transfusion was required for them. There was no statistically significant difference according to gestational age in mode of delivery (p>0.05). There was no difference observed in mean induction to delivery interval between second and third trimester at 5% level of significance (p>0.05). In this study, the women showed drastic improvement in cervical score following induction with mifepristone and decreased repeat caesarean rate. Eventually, the length of agony of receiving dead baby was cut short without much more ailments. Hence, mifepristone may be considered as a safe, efficacious, convenient and cost-effective induction agent for labour induction in women with dead fetus in utero in previously scarred uterus.

Rheology of saliva in health and disease.

BACKGROUND: Saliva is a complex fluid that lubricates the oropharynx and facilitates chewing, swallowing, and vocalization. Viscoelasticity is critical for the ability of saliva to fulfill these functions. Xerostomia, or a sensation of dry mouth, occurs in 17-26% of the population. Although many equate xerostomia with hyposalivation, high-risk patients frequently report oral dryness in the absence of decreased salivary flow. OBJECTIVE: This study aims to determine if xerostomia is associated with alterations in the rheological properties of saliva in addition to decreased salivary production. METHODS: The study population included patients with post-radiation xerostomia, patients with anticholinergic-induced xerostomia and healthy controls. Salivary volumetric flow rate was measured, shear viscosity was measured using oscillatory rheometry, and extensional viscosity was measured using capillary thinning methods. Groups were compared using descriptive statistics and univariate analysis. RESULTS: A total of 36 subjects were included: 15 with post-radiation xerostomia, 9 with anticholinergic-induced xerostomia and 12 controls. Salivary volumetric flow was significantly decreased in post-radiation and anticholinergic-induced patients compared to controls. On capillary thinning testing, saliva from xerostomia patients had significantly greater extensional viscosity compared to controls. However, saliva from the three groups showed no significant difference in the complex viscosity or the storage or loss modulus of saliva with oscillatory rheology. CONCLUSIONS: Xerostomia is associated with decreased salivary volumetric flow and quantitative changes in the rheologic properties of saliva.

Clinical and Demographic Predictor of the Advanced Stage of Carcinoma Cervix in a Tertiary Level Hospital of Bangladesh.

Though cervical cancer is a preventable disease it is the most progressive and devastating diseases posing a threat of mortality for women of developing countries. Majority of the cases present to hospital at advanced stage when treatment is less feasible. Objective is to determine the factors associated with the advanced stage presentation to the hospital, socio-demographic factor, patterns of complications and histological types among patients with carcinoma cervix. This was an observational descriptive type of cross-sectional study carried out in the department of Obstetrics and Gynecology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from 15 January to 27 September 2017. Women who were newly confirmed to have cervical cancer by histology were enrolled. Stages IIB and above was considered as advanced disease. The patients were interviewed face to face by the researcher for the purpose of collection of data. Then the patients were examined by the researcher for certain sings and those would be recorded in the check-list. Histopathological report was noted in data collection sheet. In this study data analysis was done by SPSS version 22.0. Total 66 clinically and histologically confirmed advanced ca-cervixes were taken up during this study. Most common stage was stage III, 49(74.2%) out of 66 population. Majority of female were found 34(51.5%) in age group 51-60. More than half of population 54(81.8%) were living with their husband and 12(18.1%) were widow at the time of study. High level of illiteracy among women and their problematic health seeking behavior for gynecological symptoms are responsible for advanced diagnosis of cervical cancer.

Interventions for sleep difficulties in adults with an intellectual disability: a systematic review.

BACKGROUND: Current literature highlights higher prevalence rates of sleep difficulties amongst adults with an intellectual disability. However, no synthesis has been conducted to assess the effectiveness of existing interventions in this population. Thus, the aim of this review was to assess the effectiveness of sleep interventions in adults with an intellectual disability (ID). METHOD: Eight databases were searched to identify interventions for sleep difficulties amongst adults with an ID. The study quality was assessed with the Risk Of Bias In Non-randomised Studies - of Interventions. Nine studies (n = 97) were eligible for inclusion in the review. RESULTS: There was a notable study on heterogeneity in terms of the population, study design, intervention studied, sleep assessment and outcome assessments used. Eight of the nine studies reported improvement in sleep following intervention. However, these findings need additional support as only 97 participants involving a variety of interventions and measurement systems were used across all studies. Furthermore, eight of the nine studies had serious to critical risk of bias. The only study identified as having low risk of bias was a placebo-controlled randomised controlled trial for the use of melatonin. CONCLUSIONS: This review highlights the need for objective measures such as actigraphy and studies with greater experimental control investigating sleep interventions in adults with ID.

Medialisation thyroplasty with tensor fascia lata: a novel approach for reducing post-thyroplasty complications.

BACKGROUND: Medialisation thyroplasty is considered the 'gold standard' treatment for unilateral vocal fold paralysis, enabling improvement of voice and swallowing function, and preventing life-threatening aspiration events. The most commonly used laryngeal implants induce some degree of local tissue inflammatory response, and carry the risk of immediate or delayed implant extrusion. METHODS: This paper describes a novel approach for medialisation thyroplasty. Specifically, it utilises a ribbon of autologous tensor fascia lata harvested at the time of surgery. This is layered within the paraglottic space in a manner similar to Gore-Tex thyroplasty. RESULTS: Thus far, this method has been accomplished in two patients with unilateral vocal fold paralysis, who also received prior radiotherapy to the head and neck. CONCLUSION: Given the increased risk of post-operative wound breakdown and infection in irradiated patients, it is suggested that this new approach will lead to improved outcomes, and a decrease in complications such as extrusion or wound infection, particularly in this patient population.

Proposed anti-HSV compounds isolated from Simira species.

Secondary metabolites isolated from Simira eleiezeriana and Simira glaziovii were evaluated against herpes simplex virus (HSV-1) and (HSV-2). The 50% effective concentrations values (EC50) were calculated from the dose-response curve and the selectivity index (SI) against the virus. The physicochemical data LogP, (PSA), (NRB), (HBA) and (HBD) were obtained using Marvin Sketch. Among the tested compounds, conipheraldeyde, harman and simirane A showed better results with EC50 6.39; 4.90; 4.61 µg/mL and SI 78.3; 11.8; 7.01, respectively, for HSV-1, and EC50 41.2; 71.8; 3.73 µg/mL and SI 12.1; 24.7; 8.7, respectively, for HSV-2. The percentage of inhibition (PI) obtained for HSV-1 were higher than 60%, and for HSV-2 these compounds showed PI > 90%. The physical chemical data showed that the most active compounds satisfy the attributes for drugs with good oral bioavailability.

Surgical management of colonic basidiobolomycosis among adolescent and adult patients: presentation and outcome.

AIM: The aim of this study was to review retrospectively the clinical presentations, indications for surgery and surgical outcomes of adolescent and adult patients who were diagnosed with colonic basidiobolomycosis in the last 10 years. METHOD: The study was carried out in Aseer Central Hospital, Abha, Saudi Arabia by reviewing the medical files of all patients in the last 10 years who were diagnosed with colonic basidiobolomycosis and required surgical intervention. RESULTS: There were 22 patients. Common findings in all patients were weight loss, abdominal pain and an abdominal mass. The right colon was affected in 21 patients. The initial diagnosis was correct in seven patients while nine were thought to be malignant. All patients underwent colonic resection followed by at least 1 year of antifungal medical treatment. Intra-operatively, all patients had moderate or dense adhesions, an abdominal mass and lymphadenopathy. Most surgeons had the impression intra-operatively that the diagnosis was inflammatory rather than malignant. Postoperatively, three patients died within 6 months of the operation due to progression of the disease. Four patients developed severe wound infections, three of whom had abdominal dehiscence and required re-closure. CONCLUSION: Colonic basidiobolomycosis is a life-threatening fungal infection that should be considered a surgical condition. A high index of suspicion including basidiobolomycosis in the differential diagnosis for the acute abdomen with a colonic mass is required for a proper diagnosis. Early aggressive surgical management followed by a prolonged course of itraconazole postoperatively could improve the outcome of the condition.

Risk factors for adult acquired subglottic stenosis.

OBJECTIVE: The aetiology and outcomes for patients with acquired subglottic stenosis are highly variable. This study aimed to identify risk factors for subglottic stenosis and patient characteristics that predict long-term clinical outcomes. METHODS: A retrospective review was performed on 63 patients with subglottic stenosis and 63 age-matched controls. Patient demographics and clinical characteristics were compared. Subglottic stenosis patients were further grouped according to tracheostomy status (i.e. tracheostomy never required, tracheostomy initially required but patient eventually decannulated, and tracheostomy-dependent). Patient factors from these three groups were then compared to evaluate risk factors for long-term tracheostomy dependence. RESULTS: Compared to controls, patients with subglottic stenosis had a significantly higher body mass index (30.8 vs 26.0 kg/m2; p < 0.001) and were more likely to have diabetes (23.8 per cent vs 7.94 per cent; p = 0.01). Comparing tracheostomy outcomes within the subglottic stenosis group, body mass index trended towards significance (p = 0.08). Age, gender, socio-economic status, subglottic stenosis aetiology and other co-morbidities did not correlate with outcome. CONCLUSION: Obesity and diabetes are significant risk factors for acquiring subglottic stenosis. Further investigations are required to determine if obesity is also a predictor for failed tracheostomy decannulation in subglottic stenosis.

Anticholinergic medication use is associated with globus pharyngeus.

BACKGROUND: Globus pharyngeus has been linked to salivary hypofunction. We hypothesise that a considerable portion of the globus experienced by patients is due to a drying effect secondary to anticholinergic medication use; this study aimed to determine their association. METHODS: A cross-sectional study was conducted of 270 patients who presented to a laryngology practice over 6 months. Participants rated globus sensation on a 5-point severity scale, with those scoring 0 considered as controls (non-globus). Participants were excluded if they had a likely cause of globus. Scores were compared with participants' medication lists, co-morbidities, age and gender, and evaluated using multivariate analysis, with significance set at p < 0.05. RESULTS: Any participant taking at least 2 anticholinergic medications had a 3.52 increased odds (p = 0.02) of experiencing globus. A previous diagnosis of gastroesophageal reflux disease was also significantly associated with globus (p = 0.004), with an odds ratio of 3.75. CONCLUSION: A substantial portion of idiopathic globus may be due to anticholinergic use or reflux. The findings implicate medication use as a risk factor for globus. An awareness of these associations is invaluable for identifying cause and treating globus.

A murine model of subglottic granulation.

OBJECTIVE: This study aimed to develop a functional model of subglottic stenosis by inducing direct airway irritation in transplanted mouse laryngotracheal complexes. METHODS: Laryngotracheal complexes from C57BL/6 mice were harvested and divided into three groups: uninjured, mechanically injured and chemically injured. Donor laryngotracheal complexes from each group were placed in dorsal subcutaneous pockets of recipient mice. Each week, the transplanted laryngotracheal complexes were harvested, and tissues were fixed, sectioned, and stained with haematoxylin and eosin. Representative slides were reviewed by a blinded pathologist, to determine the formation of granulation tissue, and graded as to the degree of granulation formation. RESULTS: Direct airway irritation induced granulation tissue formation under the disrupted epithelium of airway mucosa; this was seen as early as two weeks after chemical injury. CONCLUSION: Results indicate that granulation tissue formation in a murine model may be an efficient tool for investigating the development and treatment of subglottic stenosis.

You can't pay me to quit: the failure of financial incentives for smoking cessation in head and neck cancer patients.

OBJECTIVE: A prospective randomised study was conducted at a tertiary care hospital to evaluate the effects of financial incentives for smoking cessation targeted at a high-risk population. METHODS: Patients with a past history of head and neck cancer were voluntarily enrolled over a two-year period. They were randomised to a cash incentives or no incentive group. Subjects were offered enrolment in smoking cessation courses. Smoking by-product levels were assessed at 30 days, 3 months and 6 months. Subjects in the incentive group received $150 if smoking cessation was confirmed. RESULTS: Over 2 years, 114 patients with an established diagnosis of head and neck cancer were offered enrolment. Twenty-four enrolled and 14 attended the smoking cessation classes. Only two successfully quit smoking at six months. Both these patients were in the financially incentivised group and received $150 at each test visit. CONCLUSION: Providing a financial incentive for smoking cessation to a population already carrying a diagnosis of head and neck cancer in order to promote a positive behaviour change was unsuccessful.

Plasma cell-rich acute rejections in living-related kidney transplantation: a clinicopathological study of 50 cases.

BACKGROUND: Acute rejections (ARs) with plasma cell-rich infiltrates (PCARs) are associated with poor outcomes. PATIENTS AND METHODS: Between February 2012 and December 2013, 1630 dysfunctional renal graft biopsies were performed. Of these, 50 (3%) showed PCAR. ARs with >10% plasma cells were defined as PCAR. Human leukocyte antigen (HLA) antibodies were tested in historic sera and at the time of PCAR. Treatment for PCAR comprised methylprednisolone, antithymocyte globulin, plasmapheresis, and anti-CD20 antibody. RESULTS: Of the 1630 dysfunctional biopsies, 50 (3%) had PCAR which occurred 3.1 ± 2.55 yr after transplant. The percentage of plasma cells was 28.8 ± 11.7, and CD138, 29.0 ± 12.4. Donor-specific antibodies (DSAs) were found in 32 (64%) overall, Class I in 15% and Class II in 65%. Post-treatment serum creatinine improved from 3.80 ± 2.59 to 2.66 ± 1.59 mg/dL in DSA positive (p < 0.003) and from 2.59 ± 1.09 to 2.08 ± 0.86 mg/dL in DSA negative (p < 0.008). One- and two-yr graft survival after PCAR was 72%, 42% in the DSA-positive vs. 89%, 82% in the DSA-negative group, respectively (p = 0.071). CONCLUSIONS: Our results show that PCAR occurs late after transplant and in many cases is associated with DSAs. Graft outcome was poor when PCAR was associated with DSAs.

Translational potential of olfactory mucosa for the study of neuropsychiatric illness.

The olfactory mucosa (OM) is a unique source of regenerative neural tissue that is readily obtainable from living human subjects and thus affords opportunities for the study of psychiatric illnesses. OM tissues can be used, either as ex vivo OM tissue or in vitro OM-derived neural cells, to explore parameters that have been difficult to assess in the brain of living individuals with psychiatric illness. As OM tissues are distinct from brain tissues, an understanding of the neurobiology of the OM is needed to relate findings in these tissues to those of the brain as well as to design and interpret ex vivo or in vitro OM studies. To that end, we discuss the molecular, cellular and functional characteristics of cell types within the olfactory mucosa, describe the organization of the OM and highlight its role in the olfactory neurocircuitry. In addition, we discuss various approaches to in vitro culture of OM-derived cells and their characterization, focusing on the extent to which they reflect the in vivo neurobiology of the OM. Finally, we review studies of ex vivo OM tissues and in vitro OM-derived cells from individuals with psychiatric, neurodegenerative and neurodevelopmental disorders. In particular, we discuss the concordance of this work with postmortem brain studies and highlight possible future approaches, which may offer distinct strengths in comparison to in vitro paradigms based on genomic reprogramming.

Mapping the HLA ligandome landscape of acute myeloid leukemia: a targeted approach toward peptide-based immunotherapy.

Identification of physiologically relevant peptide vaccine targets calls for the direct analysis of the entirety of naturally presented human leukocyte antigen (HLA) ligands, termed the HLA ligandome. In this study, we implemented this direct approach using immunoprecipitation and mass spectrometry to define acute myeloid leukemia (AML)-associated peptide vaccine targets. Mapping the HLA class I ligandomes of 15 AML patients and 35 healthy controls, more than 25 000 different naturally presented HLA ligands were identified. Target prioritization based on AML exclusivity and high presentation frequency in the AML cohort identified a panel of 132 LiTAAs (ligandome-derived tumor-associated antigens), and 341 corresponding HLA ligands (LiTAPs (ligandome-derived tumor-associated peptides)) represented subset independently in >20% of AML patients. Functional characterization of LiTAPs by interferon-γ ELISPOT (Enzyme-Linked ImmunoSpot) and intracellular cytokine staining confirmed AML-specific CD8(+) T-cell recognition. Of note, our platform identified HLA ligands representing several established AML-associated antigens (e.g. NPM1, MAGED1, PRTN3, MPO, WT1), but found 80% of them to be also represented in healthy control samples. Mapping of HLA class II ligandomes provided additional CD4(+) T-cell epitopes and potentially synergistic embedded HLA ligands, allowing for complementation of a multipeptide vaccine for the immunotherapy of AML.

Personalized medicine approaches in epilepsy.

Epilepsy affects 50 million persons worldwide, a third of whom continue to experience debilitating seizures despite optimum anti-epileptic drug (AED) treatment. Twelve-month remission from seizures is less likely in female patients, individuals aged 11-36 years and those with neurological insults and shorter time between first seizure and starting treatment. It has been found that the presence of multiple seizures prior to diagnosis is a risk factor for pharmacoresistance and is correlated with epilepsy type as well as intrinsic severity. The key role of neuroinflammation in the pathophysiology of resistant epilepsy is becoming clear. Our work in this area suggests that high-mobility group box 1 isoforms may be candidate biomarkers for treatment stratification and novel drug targets in epilepsy. Furthermore, transporter polymorphisms contributing to the intrinsic severity of epilepsy are providing robust neurobiological evidence on an emerging theory of drug resistance, which may also provide new insights into disease stratification. Some of the rare genetic epilepsies enable treatment stratification through testing for the causal mutation, for example SCN1A mutations in patients with Dravet's syndrome. Up to 50% of patients develop adverse reactions to AEDs which in turn affects tolerability and compliance. Immune-mediated hypersensitivity reactions to AED therapy, such as toxic epidermal necrolysis, are the most serious adverse reactions and have been associated with polymorphisms in the human leucocyte antigen (HLA) complex. Pharmacogenetic screening for HLA-B*15:02 in Asian populations can prevent carbamazepine-induced Stevens-Johnson syndrome. We have identified HLA-A*31:01 as a potential risk marker for all phenotypes of carbamazepine-induced hypersensitivity with applicability in European and other populations. In this review, we explore the currently available key stratification approaches to address the therapeutic challenges in epilepsy.

GABAA α5 subunit-containing receptors do not contribute to reversal of inflammatory-induced spinal sensitization as indicated by the unique selectivity profile of the GABAA receptor allosteric modulator NS16085.

GABAA receptor positive allosteric modulators (PAMs) mediate robust analgesia in animal models of pathological pain. Restoration of diminished spinal GABAA-α2 and -α3 subunit-containing receptor function is a principal contributor to this analgesia, albeit involvement of GABAA-α5-receptors has not been excluded. Thus, we compared NS11394 and TPA023 (PAMs with selectivity/efficacy at GABAA-α2/α3/α5 receptors) with TP003 (a reportedly GABAA-α3 selective PAM) against spinal sensitization. However, in-house electrophysiology studies designed to confirm the selectivity of TPA023 and TP003 for human GABAA receptors did not corroborate published data, with TP003 displaying considerable GABAA-α5 receptor efficacy. Therefore, we identified a novel PAM, NS16085, which possesses negligible efficacy at GABAA-α5 receptors, but with GABAA-α2/α3 efficacy equivalent to NS11394. At the GABAA-α1 receptor the compound gives low level of negative modulation further separating it from the other compounds. Rat pups with carrageenan-induced hindpaw inflammatory hyperalgesia were used to make ex vivo spinal dorsal root-evoked ventral root recordings. Some spontaneous activity and large numbers of spikes to repetitive stimulation of dorsal roots at C-fibre intensity, indicative of wind-up and sensitization were observed. Equimolar concentrations of NS11394, TP003 and NS16085 all attenuated wind-up to a similar degree; TPA023 was clearly less effective. In adult rats, NS16085 (3-30 mg/kg, p.o.) dose-dependently reduced formalin-induced hindpaw flinching with efficacy comparable to NS11394. Thus, potentiation of GABAA-α2 and-α3 receptors is sufficient to depress spinal sensitization and mediate analgesia after inflammatory injury. Positive modulation at GABAA-α5-receptors is apparently dispensable for this process, an important consideration given the role of this receptor subtype in cognitive function.

Assessment of the AAV-mediated expression of channelrhodopsin-2 and halorhodopsin in brainstem neurons mediating auditory signaling.

The physiology and circuitry associated with dorsal cochlear nucleus neurons (DCN) have been well described. The ability to remotely manipulate neuronal activity in these neurons would represent a step forward in the ability to understand the specific function of DCN neurons in hearing. Although, optogenetics has been used to study the function of pathways in other systems for several years, in the auditory system only neurons in the auditory cortex have been studied using this technique. Adeno-associated viral vectors with either channelrhodopsin-2 fused with GFP (ChR2-GFP) or halorhodopsin fused with mCherry (HaloR-mCherry), capable of expressing light sensitive cation channels or chloride pumps, respectively, were delivered into the dorsal cochlear nucleus (DCN). One to 18 months later, expression of ChR2 and HaloR was observed throughout the DCN. Rhodopsin distribution within the DCN was determined to be within several cell types identified based on morphology and location within the DCN. Expression of ChR2-GFP and HaloR-mCherry was found at both the injection site as well as in regions receiving projections from the site. Wavelength appropriate optical stimulation in vivo resulted in neuronal activity that was significantly increased over pre-stimulation levels with no return to baseline levels during the time of the light exposure. We also examined the effects of optically driven neuronal activity on subsequent tone driven responses in the DCN. In the DCN 75% of the 16 electrode sites showed decreased neuronal activity in response to a tone immediately following light stimulation while six percent were decreased following tone stimulation and 19% of the electrode sites showed no change. This is in contrast to tone driven neuronal activity prior to the light exposure in which the majority of electrode sites showed increased neuronal activity. Our results indicate that expression and activation of rhodopsin within neurons involved in auditory processing does not appear to have deleterious effects on hearing even 18 months following expression. In addition, virally targeted rhodopsins may be useful as tract tracers to delineate as well as modulate the activity of pathways and specific neurons. In the future rhodopsins can be targeted to specific subpopulations of auditory neurons. Ultimately, photostimulation may provide a physiologically relevant method for modulating the function of auditory neurons and affecting hearing outcomes. This article is part of a Special Issue entitled Optogenetics (7th BRES).

A study of subunit selectivity, mechanism and site of action of the delta selective compound 2 (DS2) at human recombinant and rodent native GABA(A) receptors.

BACKGROUND AND PURPOSE: Most GABA(A) receptor subtypes comprise 2α, 2ß and 1γ subunit, although for some isoforms, a δ replaces a γ-subunit. Extrasynaptic δ-GABA(A) receptors are important therapeutic targets, but there are few suitable pharmacological tools. We profiled DS2, the purported positive allosteric modulator (PAM) of δ-GABA(A) receptors to better understand subtype selectivity, mechanism/site of action and activity at native δ-GABA(A) receptors. EXPERIMENTAL APPROACH: Subunit specificity of DS2 was determined using electrophysiological recordings of Xenopus laevis oocytes expressing human recombinant GABA(A) receptor isoforms. Effects of DS2 on GABA concentration-response curves were assessed to define mechanisms of action. Radioligand binding and electrophysiology utilising mutant receptors and pharmacology were used to define site of action. Using brain-slice electrophysiology, we assessed the influence of DS2 on thalamic inhibition in wild-type and δ(0/0) mice. KEY RESULTS: Actions of DS2 were primarily determined by the δ-subunit but were additionally influenced by the α, but not the ß, subunit (α4/6ßxδ > α1ßxδ >> γ2-GABA(A) receptors > α4ß3). For δ-GABA(A) receptors, DS2 enhanced maximum responses to GABA, with minimal influence on GABA potency. (iii) DS2 did not act via the orthosteric, or known modulatory sites on GABA(A) receptors. (iv) DS2 enhanced tonic currents of thalamocortical neurones from wild-type but not δ(0/0) mice. CONCLUSIONS AND IMPLICATIONS: DS2 is the first PAM selective for α4/6ßxδ receptors, providing a novel tool to investigate extrasynaptic δ-GABA(A) receptors. The effects of DS2 are mediated by an unknown site leading to GABA(A) receptor isoform selectivity.

Current intraoperative devices to reduce visual loss after spine surgery.

Postoperative visual loss (POVL) after spine surgery performed with the patient prone is a rare but devastating postoperative complication. The incidence and the mechanisms of visual loss after surgery are difficult to determine. The 4 recognized causes of POVL are ischemic optic neuropathy (approximately 89%), central retinal artery occlusion (approximately 11%), cortical infarction, and external ocular injury. There are very limited guidelines or protocols on the perioperative practice for "prone-position" surgeries. However, new devices have been designed to prevent mechanical ocular compression during prone-position spine surgeries. The authors used PubMed to perform a literature search for devices used in prone-position spine surgeries. A total of 7 devices was found; the authors explored these devices' features, advantages, and disadvantages. The cause of POVL seems to be a multifactorial problem with unclear pathophysiological mechanisms. Therefore, ocular compression is a critical factor, and eliminating any obvious compression to the eye with these devices could possibly prevent this devastating perioperative complication.