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Background/Objectives: Left ventricular diastolic dysfunction (LVDD) and elevated left ventricular filling pressure (LVFP) are strong predictors of clinical outcomes across various populations. However, their diagnostic utility in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that LVDD with elevated LVFP (based on echocardiography) was more likely to be prevalent in ESUS compared to non-cardioembolic stroke (NCE) and to be associated with atrial fibrillation (AF) on follow-up monitoring. Methods: This is a single-center retrospective study that included adult patients with a diagnosis of acute ischemic stroke between January 2016 and June 2017. LV function was assessed by inpatient transthoracic echocardiogram (TTE), and stroke etiology was adjudicated by the neurologist per the consensus criteria. Patients with cardioembolic stroke and those with indeterminate diastolic function on TTE were excluded. Baseline patient characteristics and clinical variables were compared among patients with and without LVDD and elevated LVFP. Multivariable regression models were used to assess the associations between diastolic dysfunction, ESUS, and AF detection in ESUS patients. Results: We identified 509 patients with ESUS and NCE stroke who had reported diastolic function. The mean age was 64.19 years, 45.19% were female, and 146 had LVDD with available LVFP data. LVDD was not associated with ESUS (adjusted OR: 1.43, 95% CI: 0.90–2.27, p = 0.130) or atrial fibrillation (AF) detection on cardiac monitoring (adjusted OR: 1.88, 95% CI: 0.75–4.72, p = 0.179). However, LVDD with elevated LVFP was borderline associated with ESUS (adjusted OR: 2.17, 95% CI: 0.99–4.77, p = 0.054) and significantly associated with AF detection (adjusted OR: 3.59, 95% CI: 1.07–12.06, p = 0.038). Conclusions: Our data suggest that LVDD with elevated LVFP is borderline associated with ESUS and significantly associated with AF detection on follow-up cardiac monitoring. Therefore, the presence of LVDD with an increased probability of elevated LVFP may help identify a subset of stroke patients more likely to have ESUS, potentially due to atrial cardiopathy with underlying occult AF. Further studies are needed to confirm our findings and to evaluate the safety and efficacy of anticoagulation in patients with ESUS and LVDD with elevated LVFP. [ABSTRACT FROM AUTHOR]

Background: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. Methods: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow‐up detection of AF in ESUS patients. Results: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266–2.986, p =.002), contractile (aOR 1.568, 95% CI 1.035–2.374, p =.034), and conduit strain (aOR 2.288, 95% CI 1.448–3.613, p =.001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029–6.236, p =.043), contractile strain (OR 2.828, 95% CI 1.158–6.903, p =.022), and conduit strain (OR 2.614, 95% CI 1.003–6.815, p =.049) were significantly associated with subsequent detection of AF. Conclusion: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies. [ABSTRACT FROM AUTHOR]

Objective: Anticoagulation therapy is commonly interrupted in patients with atrial fibrillation (AF) for elective procedures. However, the risk factors of acute ischemic stroke (AIS) during the periprocedural period remain uncertain. We performed a nationwide analysis to evaluate AIS risk factors in patients with AF undergoing elective surgical procedures. Methods: Using the Nationwide Readmission Database, we included electively admitted adult patients with AF and procedural Diagnosis‐Related Group codes from 2016 to 2019. Diagnoses were identified based on International Classification of Disease, 9th revision‐Clinical Modification (ICD‐10 CM) codes. We constructed a logistic regression model to identify risk factors and developed a new scoring system incorporating CHA2DS2VASc to estimate periprocedural AIS risk. Results: Of the 1,045,293 patients with AF admitted for an elective procedure, the mean age was 71.5 years, 39.2% were women, and 0.70% had a perioperative AIS during the index admission or within 30 days of discharge. Active cancer (adjusted OR [aOR] = 1.58, 95% confidence interval [CI] = 1.42–1.76), renal failure (aOR = 1.14, 95% CI = 1.04–1.24), neurological surgery (aOR = 4.51, 95% CI = 3.84–5.30), cardiovascular surgery (aOR = 2.74, 95% CI = 2.52–2.97), and higher CHA2DS2VASc scores (aOR 1.25 per point, 95% CI 1.22–1.29) were significant risk factors for periprocedural AIS. The new scoring system (area under the receiver operating characteristic curve [AUC] = 0.68, 95% CI = 0.67 to 0.79) incorporating surgical type and cancer outperformed CHA2DS2VASc (AUC = 0.60, 95% CI = 0.60 to 0.61). Interpretation: In patients with AF, periprocedural AIS risk increases with the CHA2DS2VASc score, active cancer, and cardiovascular or neurological surgeries. Studies are needed to devise better strategies to mitigate perioperative AIS risk in these patients. ANN NEUROL 2023;94:321–329 [ABSTRACT FROM AUTHOR]

Background: Headache is a common presenting symptom of intracerebral hemorrhage (ICH) and often necessitates treatment with opioid medications. However, opioid prescribing patterns in patients with ICH are not well described. We aimed to characterize the prevalence and risk factors for short and longer-term opioid use in patients with ICH. Methods: We conducted a retrospective cohort study using data from a single-center registry of patients with nontraumatic ICH. This registry included data on demographics, ICH-related characteristics, and premorbid, inpatient, and postdischarge medications. After excluding patients who died or received end-of-life care, we used multivariable regression models adjusted for premorbid opioid use to determine demographic and ICH-related risk factors for inpatient and postdischarge opioid use. Results: Of 468 patients with ICH in our cohort, 15% (n = 70) had premorbid opioid use, 53% (n = 248) received opioids during hospitalization, and 12% (n = 53) were prescribed opioids at discharge. The most commonly used opioids during hospitalization were fentanyl (38%), oxycodone (30%), morphine (26%), and hydromorphone (7%). Patients who received opioids during hospitalization were younger (univariate: median [interquartile range] 64 [53.5–74] vs. 76 [67–83] years, p < 0.001; multivariable: odds ratio [OR] 0.96 per year, 95% confidence interval [CI] 0.94–0.98) and had larger ICH volumes (univariate: median [interquartile range] 10.1 [2.1–28.6] vs. 2.7 [0.8–9.9] cm3, p < 0.001; multivariable: OR 1.05 per cm3, 95% CI 1.03–1.08) than those who did not receive opioids. All patients who had external ventricular drain placement and craniotomy/craniectomy received inpatient opioids. Additional risk factors for increased inpatient opioid use included infratentorial ICH location (OR 4.8, 95% CI 2.3–10.0), presence of intraventricular hemorrhage (OR 3.9, 95% CI 2.2–7.0), underlying vascular lesions (OR 3.0, 95% CI 1.1–8.1), and other secondary ICH etiologies (OR 7.5, 95% CI 1.7–32.8). Vascular lesions (OR 4.0, 95% CI 1.3–12.5), malignancy (OR 5.0, 95% CI 1.5–16.4), vasculopathy (OR 10.0, 95% CI 1.8–54.2), and other secondary etiologies (OR 7.2, 95% CI 1.8–29.9) were also risk factors for increased opioid prescriptions at discharge. Among patients who received opioid prescriptions at discharge, 43% (23 of 53) continued to refill their prescriptions at 3 months post discharge. Conclusions: Inpatient opioid use in patients with ICH is common, with some risk factors that may be mechanistically connected to primary headache pathophysiology. However, the lower frequency of opioid prescriptions at discharge suggests that inpatient opioid use does not necessarily lead to a high rate of long-term opioid dependence in patients with ICH. [ABSTRACT FROM AUTHOR]

Despite ongoing local and international peace efforts, the Jews, Arabs, and other residents of Israel and the Palestinian territories (i.e., the West Bank and Gaza) have endured decades of political, social, and physical upheaval, with periodic eruptions of violence. It has been theorized that the psychological impact of the Israeli–Palestinian conflict extends beyond the bounds of psychiatric disorders such as posttraumatic stress disorder (PTSD). Exposure to the ongoing conflict may lead to changes in the way Israelis and Palestinians think, feel, and act; while these changes may not meet the thresholds of PTSD or depression, they nonetheless could have a strong public health impact. It is unclear whether existing studies have found associations between exposure to the conflict and nonclinical psychological outcomes. We conducted a systematic review to synthesize the empirical research on the Israeli–Palestinian conflict and its psychological consequences. As a whole, the body of literature we reviewed suggests that exposure to regional political conflict and violence may have detrimental effects on psychological well-being and that these effects likely extend beyond the psychiatric disorders and symptoms most commonly studied. We found evidence that exposure to the conflict informs not only the way Israelis and Palestinians think, feel, and act but also their attitudes toward different religious and ethnic groups and their degree of support for peace or war. We also found that Palestinians may be at particularly high risk of experiencing psychological distress as a result of the conflict, though more research is needed to determine the extent to which this is due to socioeconomic stress. Our review suggests the need for more studies on the nonclinical psychological aspects of the Israeli–Palestinian conflict as well as for longitudinal studies on the impact of the conflict on both Israelis and Palestinians. [ABSTRACT FROM AUTHOR]

Hypoxia elevates splanchnic sympathetic nerve activity (SNA) with differential effects during inspiration and expiration by unresolved central mechanisms. We examined the hypothesis that cardiovascular-related neurones in the caudal ventrolateral medulla (CVLM) contribute to the complex sympathetic response to hypoxia. In chloralose-anaesthetized, ventilated, vagotomized rats, acute hypoxia (10% O2, 60 s) evoked an increase in SNA (103 ± 12%) that was characterized by a decrease in activity during early inspiration followed by a prominent rise during expiration. Some recorded baro-activated CVLM neurones ( n= 13) were activated by hypoxia, and most of these neurones displayed peak activity during inspiration that was enhanced during hypoxia. In contrast, other baro-activated CVLM neurones were inhibited during hypoxia ( n= 6), and most of these neurones showed peak activity during expiration prior to the onset of hypoxia. Microinjection of the glutamate antagonist kynurenate into the CVLM eliminated the respiratory-related fluctuations in SNA during hypoxia and exaggerated the magnitude of the sympathetic response. In contrast, microinjection of a GABAA antagonist (bicuculline or gabazine) into the CVLM dramatically attenuated the sympathetic response to hypoxia. These data suggest the response to hypoxia in baro-activated CVLM neurones is related to their basal pattern of respiratory-related activity, and changes in the activity of these neurones is consistent with a contribution to the respiratory-related sympathetic responses to hypoxia. Furthermore, both glutamate and GABA in the CVLM contribute to the complex sympathetic response to acute hypoxia. [ABSTRACT FROM AUTHOR]

GABAergic neurons in the caudal ventrolateral medulla (CVLM) are driven by baroreceptor inputs relayed via the nucleus tractus solitarius (NTS), and they inhibit neurons in rostral ventrolateral medulla to reduce sympathetic nerve activity (SNA) and arterial pressure (AP). After arterial baroreceptor denervation or lesions of the NTS, inhibition of the CVLM continues to increase AP, suggesting additional inputs also tonically activate the CVLM. This study examined whether the NTS contributes to baroreceptor-independent drive to the CVLM and whether glutamate promotes baroreceptor- and NTS-independent activation of the CVLM to tonically reduce SNA. In addition, we evaluated whether altering central respiratory drive, a baroreceptor-independent regulator of CVLM neurons, influences glutamatergic inputs to the CVLM. Splanchnic SNA and AP were measured in chloralose-anesthetized, ventilated, paralyzed rats. The infusion of nitroprusside decreased AP below threshold for baroreceptor afferent firing (<50 mmHg) and increased SNA to 209 ± 22% (P < 0.05), but the subsequent inhibition of the NTS by microinjection of the GABAA agonist muscimol did not further increase SNA. In contrast, after inhibition of the NTS, blockade of glutamatergic inputs to CVLM by microinjection of kynurenate increased SNA (274 ± 54%; P < 0.05; n = 7). In vagotomized rats with baroreceptors unloaded, inhibition of glutamatergic inputs to CVLM evoked a larger rise in SNA when central respiratory drive was increased (219 ± 16% vs. 271 ± 17%; n = 5; P < 0.05). These data suggest that baroreceptor inputs provide the major drive for the NTS-mediated excitation of the CVLM. Furthermore, glutamate tonically activates the CVLM to reduce SNA independent of the NTS, and this excitatory input appears to be affected by the strength of central respiratory drive. [ABSTRACT FROM AUTHOR]

Adult obese Zucker rats (OZRs) have elevated sympathetic vasomotor tone and arterial pressure (AP) with blunted baroreflex-mediated changes in heart rate (HR) compared with adult lean Zucker rats (LZRs). The present study examined whether compromised cardiac baroreflexes are indicative of attenuated sympathetic responses. In addition, because juvenile OZRs have a normal mean AP, we determined whether baroreflexes are fully functional prior to hypertension. At 13 wk, adult OZRs had an elevated baseline mean AP compared with LZRs (137 ± 3 vs. 123 ± 5 mmHg, P < 0.05) under urethane anesthesia. Phenylephrine-induced increases in AP evoked smaller inhibitions of splanchnic sympathetic nerve activity (SNA) and HR in OZRs compared with LZRs. In addition, sympathoexcitatory responses to nitroprusside-induced hypotension were also blunted in OZRs. Sigmoid analysis revealed a decreased gain, a higher mean AP at the midpoint of the curve (AP50), and a reduced range of changes in SNA in OZRs. In contrast, at 7 wk of age, although juvenile OZRs weighed more than LZRs (313 ± 13 vs. 204 ± 4 g, P < 0.05), mean AP was comparable in both groups (122 ± 5 vs. 121 ± 4 mmHg, not significant). In these rats, rapid changes in AP evoked comparable changes in SNA and HR in OZRs and LZRs. Sigmoid analysis revealed that, although the gain of the reflex was blunted in OZRs (P < 0.05), the mean AP50 and range of changes in SNA were comparable in OZRs and LZRs. Together, these data indicate that in adult OZRs, sympathetic responses to acute changes in AP are smaller than those observed in adult LZRs and that impairment of baroreceptor reflexes in OZR is not limited to the regulation of HR but extends to sympathetic vasomotor control. In addition, most of these deficits in baroreflex control of SNA develop in adulthood long after the onset of obesity and when other deficits in cardiovascular regulation are present. [ABSTRACT FROM AUTHOR]

The sympathetic nerves that maintain blood pressure are modulated by the central respiratory generator. Neurones in the rostral ventrolateral medulla (RVLM) that drive this sympathetic nerve activity (SNA) also display central respiratory drive (CRD)-related activity, suggesting integration of respiratory and cardiovascular regulatory systems within the brainstem. Whether CRD-related activity in the RVLM is due to direct inputs from central respiratory neurones or modulation of cardiovascular-related neurones that influence the RVLM is not known. The caudal ventrolateral medulla (CVLM) contains GABAergic neurones that tonically inhibit presympathetic RVLM neurones and are essential for the production of numerous cardiovascular reflexes. The present study sought to determine whether cardiovascular-related GABAergic neurones in the CVLM display CRD-related activity. The firing patterns of individual barosensitive CVLM neurones were examined in relation to phrenic nerve activity in chloralose-anaesthetized, ventilated, neuromuscularly blocked, vagotomized rats. Histograms of phrenic-triggered CVLM neuronal activity showed that all baro-activated CVLM neurones displayed one of four patterns of CRD-related activity: (i) inspiratory peak ( n= 15), (ii) inspiratory depression ( n= 15), (iii) inspiratory peak with postinspiratory depression ( n= 10), and (iv) postinspiratory peak ( n= 9). A subset of each type of CVLM neurone was identified as GABAergic by individually filling the recorded neurone with biotinamide and observing expression of GAD67 mRNA by in situ hybridization ( n= 10). These data suggest that the activity of GABAergic neurones in the CVLM is regulated by cardiovascular and respiratory inputs, and baro-activated GABAergic CVLM neurones may contribute to CRD-related modulation of presympathetic RVLM neurones and SNA. [ABSTRACT FROM AUTHOR]

Discusses the role of H.V. Evatt in the adoption of the proposal in 1947 to partition the British Mandate of Palestine into Arab and Jewish states with an internationalized zone for Jerusalem, Bethlehem and the Holy Places. Ways in which Evatt piloted partition through the United Nations Ad Hoc Committee on the Palestinian Question; Relationship with the Jews in Australia; Disorder and Arab threats of armed intervention in Palestine that followed in the wake of the partition resolution.

Examines the involvement of Australia in the emergence and successful passage of the United Nations General Assembly resolution for the partition of Palestine. Attempt to ascertain the motives and character of Australia's involvement through the country's Minister for External Affairs Doctor H.V. Evatt; Discussion on the performance of Evatt.

Hypoxia elevates splanchnic sympathetic nerve activity (SNA) with differential effects during inspiration and expiration by unresolved central mechanisms. Pre-sympathetic neurons in the rostral ventrolateral medulla (RVLM), which are necessary for the sympatho-excitatory response to hypoxia, are activated by hypoxia with oscillations entrained to the respiratory cycle. GABAergic baro-activated neurons in the caudal ventrolateral medulla (CVLM) provide the major tonic inhibition to RVLM neurons and have patterns of activity related to central respiratory drive. We examined the hypothesis that CVLM neurons are influenced by hypoxia and that the nature of their response may coincide with their pattern of respiratory modulation. We recorded from 18 baroactivated CVLM neurons with respiratory-related activity in choralose-anesthetised, vagotomized, paralyzed rats. Most CVLM neurons (13/18) were activated by hypoxia induced by inhalation of 10% O2, but others (5/18) were inhibited or silenced. The response to hypoxia was related to the pattern of central respiratory-related activity (P <0.05, Chi-square). Most (11/13) hypoxia-activated CVLM neurons had inspiratory-related activity. In contrast, most (4/5) hypoxia-inhibited neurons had expiratory-related activity. These data provide the first evidence that the CVLM may contribute to the complex sympathetic responses to hypoxia. [ABSTRACT FROM AUTHOR]