Highlights from the Tenth International Workshop on HIV Persistence during Therapy, December 13-16, 2022, Miami, Florida-USA.

The International Workshop on HIV Persistence during Therapy provides a forum in which HIV/AIDS researchers gather to share the latest research findings related to viral reservoirs and cure. The Tenth Workshop, which was attended by over 400 delegates, extended over 4 days and comprised eight sessions covering topics from the basic science of viral persistence to therapeutic approaches to HIV cure. Furthermore, satellite sessions on the first day of the Conference featuring cure research endeavours being pursued by the Bill and Melinda Gates Foundation as well as those being coordinated under the National Institutes of Health Martin Delaney Collaboratory program, provided important updates on research advances being made in these initiatives. As with previous conferences, the International Workshop on HIV Persistence during Therapy is primarily abstract-driven with only one invited talk for each of the sessions. This format, therefore, increases the number of presentations from early-stage investigators. Furthermore, presentations by Community representatives illustrated approaches to creating cure research literacy with effective messaging for the Community. The following article offers a synopsis of the meeting sessions. Due to space constraints, some presentations may have only been briefly discussed. Nevertheless, the Workshop abstracts can be found online (https://www/sciencedirect.com/journal/journal-of-virus-eradication/vol/8/suppl/S).

Neuronal desynchronization as marker of an impaired brain network.

Synchronization is a central key feature of neural information processing and communication between different brain areas. Disturbance of oscillatory brain rhythms and decreased synchronization have been associated with different disorders including schizophrenia. The aim of this study was to investigate whether synchronization (in relaxed conditions with no stimuli) between different brain areas within the delta, theta, alpha (alpha1, alpha2), beta (beta1, beta2), and gamma bands is altered in patients with a neurological disorder in order to generate significant cortical enhancements. To achieve this, we investigated schizophrenic patients (SZO; N=17, 37.5±10.4 years, 15 males) and compared them to healthy subjects (CON; N=21, 36.7±13.4 years, 15 males) applying the phase locking value (PLV). We found significant differences between SZO and CON in different brain areas of the theta, alpha1, beta2 and gamma bands. These areas are related to the central and parietal lobes for the theta band, the parietal lobe for the alpha1, the parietal and frontal for the beta2 and the frontal-central for the gamma band. The gamma band revealed the most significant differences between CON and SZO. PLV were 61.7% higher on average in SZO in most of the clusters when compared to CON. The related brain areas are directly related to cognition skills which are proved to be impaired in SZO. The results of this study suggest that synchronization in SZO is also altered when the patients were not asked to perform a task that requires their cognitive skills (i.e., no stimuli are applied - in contrast to other findings).

[Drug therapy of fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Medikamentöse Therapie des Fibromyalgiesyndroms : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A literature search for systematic reviews of randomized controlled drug trials from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: Amitriptyline and duloxetine are recommended in the case of comorbid depressive disorders or generalized anxiety disorder and pregabalin in the case of generalized anxiety disorder. Off-label use of duloxetine and pregabalin can be considered if there are no comorbid mental disorders or no generalized anxiety disorder. Strong opioids are not recommended.

[Definition, classification, clinical diagnosis and prognosis of fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Definition, Klassifikation, klinische Diagnose und Prognose des Fibromyalgiesyndroms : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A systematic search of the literature from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: The clinical diagnosis of fibromyalgia syndrome can be established by the American College of Rheumatology (ACR) 1990 classification criteria (with examination of tender points) or without the examination of tender points by the modified preliminary diagnostic ACR 2010 or 2011 criteria.

Brain activation induced by psychological stress in patients with schizophrenia.

Environmental influences are critical for the expression of genes putatively related to the behavioral and cognitive phenotypes of schizophrenia. Among such factors, psychosocial stress has been proposed to play a major role in the expression of symptoms. However, it is unsettled how stress interacts with pathophysiological pathways to produce the disease. We studied 21 patients with schizophrenia and 21 healthy controls aged 18 to 50years with 3T-fMRI, in which a period of 6min of resting state acquisition was followed by a block design, with three blocks of 1-min control-task, 1-min stress-task and 1-min rest after-task. Self-report of stress and PANSS were measured. Limbic structures were activated in schizophrenia patients by simple tasks and remained active during, and shortly after stress. In controls, stress-related brain activation was more time-focused, and restricted to the stressful task itself. Negative symptom severity was inversely related to activation of anterior cingulum and orbitofrontal cortex. Results might represent the neurobiological aspect of hyper-reactivity to normal stressful situations previously described in schizophrenia, thus providing evidence on the involvement of limbic areas in the response to stress in schizophrenia. Patients present a pattern of persistent limbic activation probably contributing to hypervigilance and subsequent psychotic thought distortions.

Induced schizophrenic like breathing pattern leads to impaired cardiorespiratory coupling in healthy subjects.

Schizophrenia is referred to as one of the most severe mental disorders in the world, and patients with this condition are associated with high cardiac mortality rates. However, the reasons for this high mortality rates are still under debate. One major contributing factor seems to be that a dysfunction of the autonomic nervous system (ANS) is evident in schizophrenia. Thereby, recent investigations focused on the analyses of respiration and cardiorespiratory coupling (CRC) in these patients.The objective of this study was to characterize the causal strength and direction of CRC applying the normalized short time partial directed coherence (NSTPDC) approach in healthy subjects (CON). In this study 25 healthy control subjects were enrolled matching in terms of age and gender to schizophrenic patients. CON were measured in resting condition (pre), breathing with schizophrenic like breathing pattern (stress) and resting condition for recovery (post). During stress CON were asked to breathe with a controlled fixed respiratory frequency, inspirationand expiration time. We found during induced stress significantly increased heart rate and reduced heart rate variability, increased breathing rate and reduced respiratory variability as well as impaired CRC for CON. In conclusion, during induced pathological breathing pattern CON exhibit an impaired and altered heart rate and respiratory regulation and CRC as indicators of a vagal withdrawal and sympathetic overdrive by the ANS. CRC analyses revealed impaired coupling strength and direction, with a driver-responder relationship from respiration to heart rate during stress. These findings support the central role of the respiratory dysregulation in schizophrenia and the assumed suppression of higher regulatory centers of the brain stem due to arousals and permanent stress situations in acute schizophrenia.

[Psychopharmacological treatment of patients in a university department of internal medicine]. / Therapie mit Psychopharmaka bei internistischen Patienten einer Universitätsklinik.

BACKGROUND AND OBJECTIVE: Psychotropic drugs are among the most widely prescribed drugs. We aimed to systematically analyze the use of psychotropic drugs among inhospital patients in a large university department of internal medicine. METHODS: All discharge letters from the Department of Internal Medicine III, University Hospital Jena, Germany, in the year 2010 were retrospectively screened for the use of psychotropic drugs. Metabolic parameters, blood pressure and blood counts were compared to those of a control group; psychiatric diagnoses and consultation of a psychiatrist were noted. RESULTS: Data from 2160 patients were examined (54.5% female, 45,5% male). In 371 patients (17.2%, 63.3% female, 36.4% male) the prescription of psychotropic drugs was recorded. The remaining 1789 patients without psychotropic drugs were used as control group. Patients with psychotropic drugs were significantly older (median 69 vs. 61 years) and more frequently female (p < 0.001). The most frequently used drug group were antidepressants. Both obesity (43.3 vs. 32.3%) and cachexia (9.1 vs. 2.8%) were significantly more common in the psychotropic drug group (p < 0.001). There were also more patients with diabetes (p < 0.001), but their HbA1c levels were not different from the control group. In 44.5% of the patients no psychiatric diagnosis was noted, in only 14.5% a psychiatrist had been consulted. Rather frequently (10% of patients) therapy with benzodiazepine receptor agonists or benzodiazepines was mentioned in the discharge letters. CONCLUSION: The indication for psychotropic drug use could not be reproduced exactly in each case. Psychiatric diagnoses lacked in a substantial part of cases. As to the rest, affective disorders and organic mental disorders were rather frequent indications. Closer interdisciplinary cooperation between internists and psychiatrists is recommended to improve psychotropic drug therapy in older, often multimorbid patients in internal medical wards.

Altered cardiovascular coupling in patients with sudden sensorineural hearing loss in comparison to healthy subjects.

The causes of idiopathic sudden sensorineural hearing loss (SSNHL) are still unclear while SSNHL seems to be a multicausal disease. To date limited information about autonomic regulation and, especially, cardiovascular coupling (CVC) are available for those patients. The objective of this study was to characterize short-term (30 min) CVC in 23 SSNHL patients in comparison to 23 healthy age and gender matched normal hearing control subjects (CON). Further on, the results from CVC should be compared with those from standard heart rate variability (HRV) and blood pressure variability (BPV) analyses. The results showed that HRV is not affected by the disease whereas BPV analysis revealed significant differences between both groups (p<0.01) whereby SSNHL exhibit a decreased short-term BPV. Results from CVC analysis demonstrated that especially the applied nonlinear methods exhibit an increased short-term CVC in SSNHL patients (p<0.01) indicating more complex interactions of short-term HR and BP regulatory processes. In conclusion, this study was the first to show a changed and decreased short-term BPV and increased nonlinear CVC in SSNHL patients. Our findings might help to improve diagnostic strategies for hearing loss caused by vascular factors.

Increased cold and heat pain thresholds influence the thermal grill illusion in schizophrenia.

BACKGROUND: Patients with schizophrenia show decreased sensitivity towards clinical and experimental painful conditions. To date, the exact underlying mechanisms are not completely understood. One method to examine central integrative processes of pain perception is the thermal grill illusion (TGI), in which interlacing cold and warm bars create the illusion of a painful sensation. METHODS: In 18 unmedicated patients with acute paranoid schizophrenia, cold and heat pain thresholds (CPT/HPT) as well as the perception of the TGI were examined and compared to 18 matched controls. In addition, symptom scales were obtained in order to relate pain perception to psychopathology. RESULTS: CPT and HPT were significantly increased in patients compared to controls. In the range of TGI stimuli that were perceived painful by controls, patients did not indicate painful sensations, instead the stimulus response curve of TGI pain perception was shifted towards higher stimulus intensities, i.e., greater temperature differentials between cold and warm bars. This increase was comparable to that seen in CPT and HPT. There was no association with psychopathology for any pain parameter. CONCLUSIONS: CPT and HPT, as well as temperature differentials for the perception of the TGI were increased in patients with schizophrenia as compared to controls. Similar to visual illusions, in which reduced contrast sensitivity has been shown to alter the perception of illusions, the discriminatory somatosensory deficit, which is reflected in higher CPT and HPT as well as the previously reported increased warmth perception thresholds, might account for the attenuation of TGI in patients.

Insular dysfunction and descending pain inhibition in anorexia nervosa.

OBJECTIVE: Reduced perception of pain is a well-established phenomenon in patients with anorexia nervosa (AN). We tested the hypothesis that altered processing of pain within the insula might account for reduced perception of pain. METHOD: Heat pain thresholds were obtained in nineteen patients with AN and matched controls. Thereafter, a thermode was used to deliver thermal painful stimuli to the right arm during functional magnetic resonance imaging (fMRI) measurements. Stimuli were initiated for 10 s from a baseline resting temperature (32°C) to three different levels (37, 42, 45°C). RESULTS: Significantly increased heat pain thresholds were observed in patients. A stronger activation during heat pain perception was found in the left posterior insula in controls. In contrast, higher levels of activity were shown in the ipsilateral pons in patients when compared to controls. In patients, we found a significant interrelation between the depression score (Beck depression inventory) and heat pain activations. CONCLUSION: We suggest that reduced activity in the left posterior insula might contribute to increased pain thresholds in patients, while increased activations in the right anterior insula and pons mirror augmented sympathetic modulation putatively related to amplification of adrenergic descending pain inhibition. In addition, pain thresholds and brain activations were influenced by disease-inherent depressed mood.

An inherited NBN mutation is associated with poor prognosis prostate cancer.

BACKGROUND: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. METHODS: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). RESULTS: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ≤ 60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. CONCLUSION: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment.

The deceleration capacity - a new measure of heart rate variability evaluated in patients with schizophrenia and antipsychotic treatment.

BACKGROUND: Schizophrenia is associated with increased cardiac mortality. A disturbed autonomic modulation of heart rate (HR) has been described in patients with schizophrenia in whom antipsychotic medication may represent an additional cardiac risk. The novel measure deceleration capacity (DC) of heart rate predicts cardiac mortality in patients with cardiovascular illnesses. The aim of the present paper was to calculate DC in patients with schizophrenia and to compare this measure with established parameters of heart rate variability (HRV). METHODS: HRV and DC were calculated in 24-hour electrocardiogram (ECG) recordings of 20 unmedicated, 40 medicated patients with schizophrenia and 40 controls. As activity has a major influence on HRV, 4-hour periods of "sleep-" and "wake-" ECG were evaluated as additional parameters. Actigraphy was used to ensure comparable levels of activity in patients and controls. RESULTS: The DC as well as the other established HRV measures were not significantly different comparing unmedicated patients with schizophrenia to healthy controls. However, medicated patients showed a significant reduction of DC calculated from ECG recordings during 4 hour over night periods. CONCLUSION: Calculation of DC might contribute to a better monitoring and identification of an increased risk of cardiac mortality in patients with schizophrenia undergoing antipsychotic treatment.

[The processing of pain in psychiatric diseases]. / Schmerzverarbeitung bei psychiatrischen Erkrankungen.

The perception and processing of pain is disturbed in many psychiatric diseases. Some diseases are known to show decreased perception of pain (e.g. borderline personality disorder), while others are associated with augmented pain perception (e.g. alcohol and drug dependence). The close relationship between psychiatric diseases and pain is most probably caused by aberrant processing of pain in brain structures, known to be involved in psychiatric disorders as well. Aberrant perception and processing of pain in patients with anorexia nervosa (AN) will be used to demonstrate this close relationship. Dysfunction within the insula has been suggested to account for many features of AN and might contribute to reduced pain perception. Moreover, it might lead to increased adrenergic descending inhibition associated with increased sympathetic modulation. Thus, pain research might be able to alter our view on autonomic regulation, which is putatively associated with increased cardiac mortality of the disease.

[Drug therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline]. / Medikamentöse Therapie des Fibromyalgiesyndroms. Systematische Übersicht und Metaanalyse.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The recommendations were based on level of evidence, efficacy (meta-analysis of the outcomes pain, sleep, fatigue and health-related quality of life), acceptability (total dropout rate), risks (adverse events) and applicability of treatment modalities in the German health care system. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: Amitriptyline and-in case of comorbid depressive disorder or generalized anxiety disorder-duloxetine are recommended. Off-label use of duloxetine and pregabalin can be considered in case of no comorbid mental disorder. Strong opioids are not recommended. The English full-text version of this article is available at SpringerLink (under "Supplemental").