International study of the Complex Stress Reaction Syndrome:Implications for transdiagnostic clinical practice

BACKGROUND The debate regarding diagnostic classification systems in psychiatry(categorial vs dimensional systems)has essential implications for the diagnosis,prevention and treatment of stress reactions.We previously found a unique pattern of stress reaction in a study executed during the coronavirus disease 2019 pandemic using large representative samples in two countries,and termed it the Complex Stress Reaction Syndrome(CSRS).AIM To investigate CSRS,Type A(psychiatric symptoms,spanning anxiety,depression,stress symptoms,and posttraumatic stress disorder(PTSD)),with or without long-coronavirus disease(COVID)residuals(CSRS,Type B,neuropsychiatric symptoms spanning cognitive deficits and fatigue,excluding systemic symptoms).Our two-tailed hypothesis was that CSRS is a condition related to an unrecognized type of stress reaction in daily life in the general population(Type A)or that it is related to the severe acute respiratory syndrome coronavirus 2 infection and its long-COVID residuals(Type B).METHODS 977 individuals in four continents(North America,Europe,Australia and the Middle East)completed the online study questionnaire in six languages using the Qualtrics platform.The study was managed by six teams in six countries that promoted the study on social media.The questionnaire assessed anxiety,depression,stress symptoms and PTSD(CSRS,Type A),cognitive deficits and fatigue(CSRS,Type B).The data were analyzed using Proportion Analyses,Multivariate Analysis of Co-Variance(MANCOVA),linear regression analyses and validated clinical cutoff points.RESULTS The results of the Proportion Analyses showed that the prevalence of 4 symptoms spanning anxiety,depression,stress symptoms,and PTSD was significantly higher than the most prevalent combinations of fewer symptoms across 4 continents,age groups,and gender.This supports the transdiagnostic argument embedded in the CSRS(Type A).The same pattern of results was found in infected/recovered individuals.The prevalence of the 4 psychiatric symptoms combination was significantly greater than that of 5 and 6 symptoms,when adding cognitive deficits and fatigue,respectively.MANCOVA showed a significant three-way interaction(age×gender×continent).Further analyses showed that the sources of this three-way interaction were threefold relating to two sub-populations at-risk:(1)Individuals that self-identified as non-binary gender scored significantly higher on all 4 psychiatric symptoms of the CSRS,Type A at young age groups(<50 years old)in North America compared to(self-identified)women and men located in the 4 continents studied,and to other ages across the adult life span;and(2)This pattern of results(CSRS,Type A)was found also in women at young ages(<40 years old)in North America who scored higher compared to men and women in other continents and other ages.Linear regression analyses confirmed the MANCOVA results.CONCLUSION These results show a combined mental health risk factor related to stress reactivity,suggesting that the CSRS is sensitive to populations at risk and may be applied to future identification of other vulnerable sub-populations.It also supports the transdiagnostic approach for more accurate prevention and treatment.Time will tell if such transdiagnostic syndromes will be part of the discussions on the next revisions of the traditional classification systems or whether the crisis in psychiatry further evolves.

Surgery for inflammatory bowel disease in the era of laparoscopy

During the course of inflammatory bowel disease (IBD), surgery may be needed. Approximately 20% of patients with ulcerative colitis (UC) will require surgery, whereas up to 80% of Crohn's disease (CD) patients will undergo an operation during their lifetime. For UC patients requiring surgery, total proctocolectomy and ileoanal pouch anastomosis (IPAA) is the operation of choice as it provides a permanent cure and good quality of life. Nevertheless a permanent stoma is a good option in selected patients, especially the elderly. Minimally invasive surgery has replaced the conventional open approach in many specialized centres worldwide. Laparoscopic colectomy and restorative IPAA is rapidly becoming the standard of care in the treatment of UC requiring surgery, whilst laparoscopic ileo-cecal resection is already the new gold standard in the treatment of complicated CD of terminal ileum. Short term advantages of laparoscopic surgery includes faster recovery time and reduced requirement for analgesics. It is, however, in the long term that minimally invasive surgery has demonstrated its superiority over the open approach. A better cosmesis, a reduced number of incisional hernias and fewer adhesions are the long term advantages of laparoscopy in IBD surgery. A reduction in abdominal adhesions is of great benefit when a second operation is needed in CD and this influences positively the pregnancy rate in young women undergoing restorative IPAA. In developing the therapeutic plan for IBD patients it should be recognized that the surgical approach to the abdomen has changed and that surgical treatment of complicated IBD can be safely performed with a true minimally invasive approach with great patient satisfaction.

Long-noncoding RNAs as epigenetic regulators in neurodegenerative diseases

The growing and rapid development of high-throughput sequencing technologies have allowed a greater understanding of the mechanisms underlying gene expression regulation.Editing the epigenome and epitranscriptome directs the fate of the transcript influencing the functional outcome of each mRNA.In this context,non-coding RNAs play a decisive role in addressing the expression regulation at the gene and chromosomal levels.Long-noncoding RNAs,consisting of more than 200 nucleotides,have been shown to act as epigenetic regulators in several key molecular processes involving neurodegenerative disorders,such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis and Huntington’s disease.Long-noncoding RNAs are abundantly expressed in the central nervous system,suggesting that their deregulation could trigger neuronal degeneration through RNA modifications.The evaluation of their diagnostic significance and therapeutic potential could lead to new treatments for these diseases for which there is no cure.

Harmonic excitation of linear respiratory mechanics for physiological dual controlled ventilation

The theoretical approach along with the rationale of harmonic excitation modality (HEM) applied as optimal dual controlled ventilation (DCV) to anaesthetized or severe brain injured patients, whose respiretory mechanics can be properly assumed steady and linear, are presented and discussed. The design criteria of an improved version of the Advanced Lung Ventilation System (ALVS), including HEM in its functional features, are described in details. In particular, the elimination of any undesiderable artificial distortion affecting the respiratory and ventilation pattern waveforms is achieved by maintaining continuous forever the airflow inside the ventilation circuit, ensuring also the highest level of safety for patient in any condition. In such a way, the full-time compatibility of controlled breathings with spontaneous breathing activity of patient during continuous positive airways pressure (CPAP) or bilevel positive airways pressure (BiPAP) ventilation modalities and during assisted/controlled ventilation(A/CV), includeing also synchronized or triggered ventilation modalities, is an intrinsic innovative feature of the system available for clinical application. As expected and according to the clinical requirements, HEM provides for physiological respiratory and ventilation pattern waveforms together with optimal “breath to breath” feedback control of lung volume driven by an improved diagnostic measurement procedure, whose outputs are also vital for adapting all the preset ventilation parameters to the current value of the respiratory parameters of patient. The results produced by software simulations concerning both adult and neonatal patients in different clinical conditions are completely consistent with those obtained by the theoretical treatment, showing that HEM reaches the best performances from both clinical and engineering points of view.

Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients

AIM: To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus (HCV) liver transplant (LT) recipients.

Detection methods and clinical significance of free peritoneal tumor cells found during colorectal cancer surgery

Peritoneal washing is now part of the standard clinical practice in several abdominal and pelvic neoplasias. However, in colorectal cancer surgery, intra-peritoneal free cancer cells(IFCC) presence is not routinely investigated and their prognostic meaning is still unclear. When peritoneal washing results are positive for the presence of IFCC a worse outcome is usually expected in these colorectal cancer operated patients, but it what is not clear is whether it is associated with an increased risk of local recurrence. It is authors' belief that one of the main reasons why IFCC are not researched as integral part of the routine staging system for colon cancer is that there still isn't a diagnostic or detection method with enough sensibility and specificity. However, the potential clinical implications of a routine research for the presence IFCC in colon neoplasias are enormous: not only to obtain a more accurate clinical staging but also to offer different therapy protocols, based on the presence of IFCC. Based on this, adjuvant chemotherapy could be offered to those patients found to be positive for IFCC; also, protocols of proactive intraperitoneal chemotherapy could be applied. Although presence of IFCC appears to have a valid prognostic significance, further studies are needed to standardize detection and examination procedures, to determine if there are and which are the stages more likely to benefit from routine search for IFCC.

Long-term results of the surgical treatment of Peyronie＇s disease with Egydio＇s technique： a European multicentre study

The long-term outcomes of 157 patients affected by Peyronie＇s disease （PD） who underwent penile straightening with Egydio＇s technique between January 2004 and December 2008 are reported. Only patients with PD who were stable for at least 6-12 months prior to surgery were enrolled in this study. Preoperative assessment included a dynamic echo colour Doppler ultrasound scan to evaluate the degree of penile deformity and the peak systolic velocity in the cavernosal arteries and an assessment of erectile function with the administration of the International Index of Erectile Function 5 （IIEF-5） questionnaire. Stretched penile length was recorded pre- and postoperatively. Surgical complications, cosmesis and sexual function, patient satisfaction and postoperative erectile function were assessed postoperatively at 3 months, I year and 2 years, respectively. After a median follow-up period of 20 months （range： 12-24 months）, we found that mild residual curvature （12%） and glans hypoesthesia （3%） were the only causes of partial dissatisfaction. No rejection of the graft was observed. All patients recovered their ability to penetrate with no difficulty. In addition, an intraoperative average increase of 2.5 cm （range： 1.7-4.1 cm） in stretched penile length was recorded, with all patients engaging in penetrative sexual intercourse. In conclusion, this procedure represents a safe and reproducible technique for the correction of penile curvature resulting from PD and yields excellent cosmetic and functional results.

Complete mesocolic excision and central vascular ligation in colorectal cancer in the era of minimally invasive surgery

Since the 19th century,appropriate lymphadenectomy has been considered a cornerstone of oncologic surgery and one of the most important prognostic factors.This approach can be applied to any surgery for gastrointestinal cancer.During surgery for colon and rectal cancer,an adequate portion of the mesentery is removed together with the segment of bowel affected by the disease.The adequate number of lymph nodes to be removed is standardized and reported by several guidelines.It is mandatory to determine the appropriate extent of lymphadenectomy and to balance its oncological benefits with the increased morbidity associated with its execution in cancer patients.Our review focuses on the concept of“complete mesenteric excision(CME)with central vascular ligation(CVL),”a radical lymphadenectomy for colorectal cancer that has gained increasing interest in recent years.The aim of this study was to evaluate the evolution of this approach over the years,its potential oncologic benefits and potential risks,and the improvements offered by laparoscopic techniques.Theoretical advantages of CME are improved local-relapse rates due to complete removal of the intact mesocolic fascia and improved distance recurrence rates due to ligation of vessels at their origin(CVL)which guarantees removal of a larger number of lymph nodes.The development and worldwide diffusion of laparoscopic techniques minimized postoperative trauma in oncologic surgery,providing the same oncologic results as open surgery.This has been widely applied to colorectal cancer surgery;however,CME entails a technical complexity that can limit its wide minimally-invasive application. This review analyzesresults of these procedures in terms of oncological outcomes, technical feasibilityand complexity, especially within the context of minimally invasive surgery.

Early onset versus late onset in Alzheimer’s disease: What is the reliable cut-off?

Objective: As the literature on conventional criteria for discriminating early-onset (EO) from late-onset (LO) Alzheimer’s disease (AD) is sparse and controversial, the aim of this study was to establish a precise age at onset (AAO) criterion, by using a specific statistical procedure, and to describe the clinical characteristics of the two sub-groups. Methods: Admixture analysis was performed to establish the AAO cut-off in a multi-center study including 2000 AD patients consecutively recruited in eight Italian Memory Clinics. None of the patients were taking acetylcholinesterase inhibitors, antipsychoticor anti-depressant drugs. At the first diagnosticvisit, they were administered the Mini Mental StateExamination, the Basic and Instrumental Activities of Daily Living and the Neuropsychiatric Inventorytoassess clinical phenomenology. Results: Using a specific statistical procedure, we established that AAO that discriminated EO-from LO-AD was 66. Compared with the LO-AD group, the EO-AD group showed longer duration of illness and a higher educational level as well as less severe functional impairment and delusions. Conclusions: Differences in sociodemographic and clinical characteristics, such as duration of illness, education and delusion severity, suggested the involvement of different pathogenic processes. Additional studies are needed to further investigate the mechanisms underlying the disorder in the two sub-groups of AD patients.

Current highlights on solid pseudopapillary neoplasm of the pancreas

Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor that predominantly affects young women in their third and fourth decade.Etiology and risk factors are unknown.Clinical symptoms are aspecific and most commonly due to mass effect.Diagnosis is made by computed tomography scan or magnetic resonance imaging and histological characterization is obtained by endoscopic ultrasound-guided fine needle biopsy.Microscopically,these lesions are composed by both solid and pseudopapillary structures with necrotic and hemorrhagic areas.Occasionally,the biological behavior is aggressive with tumor recurrence and distant metastasis.Usually,curative R0 surgical resection is the best option able to provide long term survival even in advanced disease.Unresectable disease is the main predictor of poor prognosis.Chemotherapy and radiotherapy regimens are not well standardized.However,they could be effective in reducing tumor size as neoadjuvant treatment or disease control in palliative setting.Although complete surgical resection provides a cure rate of>95%,considering young age of the patients and morbidity associated to pancreatic surgery,further studies are needed to better investigate risk factors and responsiveness to hormones in order to allow early diagnosis and follow up strategies that could avoid unnecessary surgery in less aggressive disease.

How Liquid Based Microbiology Can Change the Workflow in the Microbiology Laboratories

Liquid-based microbiology (LBM) is the future for the technological development of microbiology laboratories. In particular, the Eswab system (by Copan) simplifies and streamlines specimen collection and represents the only liquid system supporting the recovery of all types of bacteria (aerobic, anaerobic, and fastidious bacteria). In addition, LBM offers advantages in the efficiency of microorganism recovery and ease of sampling, transport, and storage. LBM also allows the introduction of true automation in the laboratory: either by using Copan ? (Walk-Away Specimen Processor) or any other commercially available specimen processor that utilizes LBM. In this paper, we illustrate how LBM can positively change laboratory workflow by illustrating several years of our experience with LBM. LBM allows clinical specimen optimization and has several important advantages: cost reduction (due to the smaller number of different devices used), time savings for medical or nursing staff (less confusion in collection device selection and fewer samples being collected), time savings for laboratory staff (fewer samples to access and handle for individual investigations), and patient comfort improvement (multiple sample collection can be avoided). A unique collection device for several investigations also guarantees quality due to the uniformity of the sample and standardization of procedures.

A Theoretical Overview of Bioresponse to Magnetic Fields on the Earth’s Surface

This survey points to the mechanisms of bioresponse caused by magnetic fields (MFs), paying attention to their action not only on ions, molecules and macromolecules, but also on cells, tissues and organisms. The significance of findings concerning the MF-dependence of cell proliferation, necrosis or apoptosis was judged by comparing the results obtained in a solenoid, where an MF can be added to the geomagnetic field (GMF), with those obtained in a magnetically shielded room, where the MFs can be attenuated or null. This comparative criterion was particularly appropriate when the differences detectable between the data provided by experimental samples and the data provided by control samples were rather small, as observed in estimating the MF-influence on total DNA replication, RNA transcription and polypeptide translation. The MF-induced inhibition of apoptosis was considered as a risk potentially leading to accumulation of cancer cells. The analysis also surveyed the MF-dependence of the interactions between host animal cells and infecting bacteria. In relation to studies on the origin and adaptation of life on the Earth, theoretical insights paving the way to elucidating the MF-interactions with biostructures and biosystems of different orders of organization evaluated the possible involvement of the so-called “biological windows”. Analogously to what is known for ionizing radiations, the efficiency of the applied MFs appeared to depend on the complexity of their biological targets.

From I Vecchi E I Giovani to Pirandellian Correspondence:A Glance at an Italy That Is Immutable in Both Its National and Its Family History

The novel I vecchi e i giovani has been the object of numerous critical interpretations,including those of Leonardo Sciascia,Gaetano Trombatore,and Massimo Onofri,in particular.Taking as its starting point Pirandello’s phrase,“la gioventùsacrificata potrebbe dare un crollo a questa oltracotante oppressione dei vecchi e prendersi finalmente uno sfogo e affermarsi vittoriosa”and applying Freudian principles,this work seeks primarily to highlight the autobiographical element that is expressed in the father/son,Luigi/Stefano,and Lando Laurentano/Stefano Landi relationships.

Semantics of Sexual Violence:The“Imperfect Victims”in the Italian Media

Starting from an etymological analysis of rape in the Indo-European language family,we want to trace the historical and semantic roots of this lexeme,in order to review its semantic and pragmatic development in the perception of Italian speakers.Our aim is to read and understand the rape victim socio-cultural stigma in collective imagination.It is therefore possible to reconstruct the lexical,socio-semiotic,and narrative domain anticipating the phenomenology of victim blaming,which characterizes the media narratives of sexual violence.The victimological profile,socially expected and culturally accepted,seems to support the original semantic connotation of the Latin word stuprum,that is“corruption of virginity”,“contamination of purity”.Many typical mainstream discourses examined,through special“gender lenses”,provide portraits of imperfect,ambiguous,unreliable victims because they are deemed guilty of not being holy enough.

Loss of homeostatic functions in microglia from a murine model of Friedreich's ataxia

Friedreich's ataxia(FRDA)is a rare genetic disorder characterized by motor discoordination and cerebellar involvement due to mutations in the frataxin(FXN)gene,which encodes a mitochondrial protein involved in ironsulfur cluster biogenesis and iron handling."While progress has been made in understanding FRDA's pathophysiology and cerebellar degeneration caused by frataxin deficiency,the role of central nervous system(CNS)-resident nonneuronal cells,as microglia,necessitates further investigation.

A Delivery Approach Modeling for Urban Freight Restocking

This paper proposes a modeling system developed in order to analyze the urban freight transport and logistics within urban and metropolitan areas. A review of models developed to simulate this segment of mobility is also reported. The review analysis highlights the limits of models for the ex-ante assessment of city logistics measures. For this reason this paper proposes a new modeling system approach for the assessment of city logistics measures. It is made of different steps approaching problems related to quantity OD （Origin-Destination） flows, restocking type OD flows, delivery OD flows, delivery OD flows for time slice and vehicle type, and vehicle OD flows. This modeling system has been specified and calibrated using some surveys carried out in the inner area of Rome where more than 500 truck drivers and more than 600 retailers have been interviewed.

意大利一项银屑病与抑郁症关系的研究

Background: Psoriasis is often associated with the risk of physical disability, social discomfort and psychological disorders. Objectives: The aim of this study was to investigate the prevalence of depressive symptomatology among Italian patients with psoriasis vulgaris, in order to better evaluate the disease severity in this patient population. Methods: Five thousand Italian patients with psoriasis were mailed the Center for Epidemiological Studies- DepressionScale (CES- D) questionnaire, a 20- item instrument developed to perform epidemiological studies of depressive symptomatology in the general population. Questionnaires with responses to 16 or more items were considered evaluable. Results: We received evaluable questionnaires from 2,391 patients, including 1,528 men (63.9% ) and 863 women (36.1% ). Depressive symptomatology was observed in 1,4822,391 patients (62% overall; females, 63% ; males, 61% ). Men<40 years of age were significantly more likely to report depressive symptoms than were men ≥ 40 years of age (67 vs. 58% , respectively; p= 0.002). Depressive symptomatology was more prevalent in psoriatic patients with only primary or secondary education than in psoriatic patients with higher education (51 vs. 32% , respectively; p<0.02). Conclusion: Our results are consistent with previous studies showing that psoriasis is associated with profound psychological morbidity, in particular with depression in a large number of patients. It is important to consider this association in the overall management of psoriasis.

Sexual outcomes after partial penectomy for penile cancer： results from a multi-institutional study

Penile cancer is an uncommon malignancy. Surgical treatment is inevitably mutilating. Considering the strong impact on patients＇ sexual life we want to evaluate sexual function and satisfaction after partial penectomy. The patients in this study （n = 25） represented all those who attended our institutions and were diagnosed and treated for penile cancer from October 2011 to November 2013. All patients underwent partial penectomy and followed-up （mean： 14 months; range： 12-25）. Sexual presurgical baseline was estimated using the International Index of Erectile Dysfunction 15 （IIEF-15）. Sexual outcomes of each patient were estimated considering four standardized and validated questionnaires. We analyzed the means and ranges of IIEF-15 including erectile function （IIEF-1-5 and -15）, orgasmic function （IIEF-9 and -10）, sexual desire （IIEF-11 and -12）, intercourse satisfaction （IIEF-6-8）, and overall satisfaction （IIEF-13 and -14）. Then, we also used Quality of Erection Questionnaire （QEQ）, Erectile Dysfunction Inventory of Treatment Satisfaction （EDITS） and Self-Esteem and Relationship （SEAR） to evaluate the sexual function and satisfaction of our patients. The final results showed that penile cancer leads to several sexual and psychosexual dysfunctions. Nevertheless, patients who undergo partial penectomy for penile cancer can maintain the sexual outcomes at levels slightly lower to those that existed in the period before surgery.