The Impact of Covid-19 Pandemic on Mental Health Services: A Comparison Between First Psychiatric Consultations Before and After the Pandemic.

Objective: A high rate of onset or exacerbation of several mental disorders has been observed during the COVID-19 pandemic. However, the risk contributing to mental distress during the pandemic remains unclear. The study aims to evaluate the risk of the onset of mental disorders by comparing the number of requests for the first psychiatric consultation before and after the COVID-19 pandemic at the psychiatric outpatient services of Varese, a small town in Northern Italy. Method: This observational retrospective study aims to compare the requests for the first psychiatric consultation at the outpatient services of Varese during the 14-month period before COVID-19 pandemic (from 1st January 2019 to 28th February 2020) versus the 14-month period after the pandemic (from 1st March 2020 to 31st May 2021) extracted from the server SIPRL-Psicheweb database (Sistema Informativo della Psichiatria, Lombardy Region). For each patient, socio-demographic features and clinical data (psychiatric diagnosis, psychiatric comorbidities, previous psychiatric records, and previous hospitalization in the psychiatric ward) were collected. Results: Three hundred ninety-five consultations were made during the pre-COVID period and 346 during the post-COVID period. No statistically significant difference was found between the number of first consultation requests in the two periods evaluated but a slight decrease in the total number during the pandemic period (395 vs 346; p=0.07) can be noticed. In the subjects of the pre-COVID group, a statistically significant association was detected with no previous psychiatric records ("absent") and with stressor-related disorders. In the post-COVID group, a statistically significant correlation between "present" previous records and anxiety-depressive disorders emerged. Conclusions: It has been observed that anxiety-depressive disorders increased in the post-COVID-19 period compared to the pre-COVID-19, instead of stressor-related disorders. This might be because stressor-related disorders may be treated by general practitioners with no psychiatric interventions. Most of the first consultations during the period of the COVID-19 pandemic were for patients who already had contact with psychiatric services.The study shows an increasing request for care by more severe patients in the first phase of the SARS-CoV-2 pandemic. Further research is needed to investigate the long-term impact of the COVID-19 pandemic on emergency departments and hospital services.

Efficacy of short-term psychodynamic psychotherapy (STPP) in depressive disorders: A systematic review and meta-analysis.

INTRODUCTION: Depression is one of the leading diseases globally. It can severely interfere with daily and occupational functioning of people affected. Both pharmacological interventions and psychotherapy are used for adult depression. The aim of the review is to evaluate the efficacy of short-term psychodynamic psychotherapy (STPP) by comparing STPP with different types of interventions. MATERIALS AND METHODS: A systematic review with meta-analysis on the efficacy of STPP in depressive disorders was performed. RESULTS: Meta-analysis findings confirm the superiority of STPP versus no interventions. The average effect size of depressive symptoms severity at the end of the treatment is -0.91 (95% CI: -1.49 - -0.33) in favor of STPP, while for clinical improvement of depressive symptoms is -0.78 (95% CI: -1.56 - 0.01). Results confirm a clear superiority of STPP to usual treatments unstructured. A mild superiority of efficacy of STPP on support psychotherapy emerged. Comparison of the efficacy of STPP vs cognitive-behavioral psychotherapy (CBT) shows little superior in case of STPP. No substantial differences in efficacy in case of STPP than control interventions emerged. Antidepressant therapy is resulted to be slightly more effective to STPP. DISCUSSION: While all the other results confirm current literature, this review shows no superiority of combined treatment than STPP only. LIMITATIONS: The review has some limitations such as the lack of moderation analysis and the high heterogenicity of the type of the studies. CONCLUSIONS: The results confirm the efficacy of STPP in depressive disorders and endorse the guidelines of National Institute for Health and Clinical Excellence (NICE).

Assessing Mental Pain as a Predictive Factor of Suicide Risk in a Clinical Sample of Patients with Psychiatric Disorders.

According to contemporary suicidology, mental pain represents one of the main suicide risk factors, along with more traditional constructs such as depression, anxiety and hopelessness. This work aims to investigate the relationship between the levels of mental pain and the risk to carry out suicide or suicide attempt in the short term in order to understand if a measurement of mental pain can be used as a screening tool for prevention. For this purpose, 105 outpatients with psychiatric diagnosis were recruited at the university hospital of Varese during a check-up visit and were assessed by using psychometric scales of mental pain levels, hopelessness, anxiety and depression. Clinical and sociodemographic variables of the sample were also collected. A period of 18 months following the recruitment was observed to evaluate any suicides or attempted suicides. Subjects numbering 11 out of 105 committed an attempted suicide. From statistical analyses, high values of the Beck Depression Inventory (BDI-II), Mental Pain Questionnaire (OMMP) and Hamilton Rating Scale for Depression (HAM-D) scales showed a significant association with the risk of carrying out a suicide attempt and, among these, OMMP and BDI-II showed characteristics of good applicability and predictivity proving suitable to be used as potential tools for screening and primary prevention of suicidal behavior.

Efficacy and tolerability of therapies set under pharmacogenetic tools suggestions: A systematic review with meta-analysis about mood disorders.

BACKGROUND: Bipolar Disorder (BD) and Major Depressive Disorder (MDD) have a huge impact on functioning and quality of life; moreover, they are linked to extensive direct and indirect costs. This systematic review with meta-analysis aims to evaluate the utility of pharmacogenetic tests (PGT) in terms of efficacy and tolerability into the routine clinical treatment of mood disorders. MATERIALS AND METHODS: The first part of the review is a qualitative overview of the PGTs used in the included studies. The second part aims to compare, in terms of efficacy and tolerability, patients affected by BD and MDD treated as usual (TAU), according to the clinicians' prescribing attitude, versus patients whose psychopharmacological treatments were set up following the PGT suggestions. RESULTS: 6 studies on MDD and 2 studies on BD were included. Regarding MDD, the meta-analysis shows a significantly higher number of patients achieving better outcome in terms of efficacy, through the evaluation of response rate and remission rate at the HDRS (Hamilton Depression Rating Scale) in the group of patients treated under the PGT suggestions; regarding BD the meta-analysis does not show any significant difference in terms of efficacy. In terms of adverse events, the available data suggest promising results about the utility of PGT to set more tolerated therapies. CONCLUSIONS: Although the limited number of studies, results confirm the importance of PGT in setting up psychopharmacological therapies as a support to clinicians' choices.

Pulmonary interstitial emphysema and complications: incidence and CT findings in COVID-19.

Background and Objectives: There are scant data available in the published literature providing chest computed tomography (CT) findings on pulmonary interstitial emphysema (PIE), complications and associated parenchymal abnormalities. We report the incidence of PIE and complications by chest CT in patients with COVID-19. Methods: We retrospective analyzed 897 chest CT scans performed with 64-slice CT scanners during the COVID-19 pandemic period from March 2020 to September 2021. Two radiologists and two physicians in training in diagnostic radiology, independently and in consensus, assessed PIE as air within the perilobular (low-attenuation area) and perivascular interstitium such as its complications, parenchymal anomalies and pleural effusion; in addition, the complications of PIE, parenchymal anomalies and pleural effusion were evaluated. Descriptive statistics were used to summarize the data, and the results were expressed as counts and percentages. Results: PIE was revealed in 25 out of 897 patients (2.8%) and associated with pneumomediastinum, subcutaneous emphysema, and pneumothorax in 25 (100%), 16 (64%), and 7 (28%), patients, respectively. Out of 25 patients, 24 patients had ground-glass opacity (GGO), 23 patients had crazy paving, 22 patients had consolidation and 2 patients had pleural effusion. Eighteen out of 25 patients had noninvasive ventilation before CT scan, initially treated with continuous positive airway pressure (positive end expiratory pressure [PEEP] of 10 cmH2O) and subsequently with bilevel positive airway pressure (range PEEP of 8-12 cmH2O). The remaining seven patients had invasive mechanical ventilation via orotracheal intubation (pressure plateau at approximately 25 cmH2O). Six out of 25 (24%) patients died. Conclusion: Chest CT allows the detection of complications associated with PIE and parenchyma abnormalities. The timely detection of PIE and minimal pneumomediastinum could aid the optimization of ventilation modalities and parameters based on patients clinical status therefore potentially reducing complications.

The North Italian innovative project for common psychiatric disorders: Evaluating the output of a treatment model of an outpatient clinic for anxiety and depression.

Depressive disorders were considered the first causes of disability worldwide as early as 2018. The outpatient clinic for anxiety and depression at the University Hospital of Varese represents a service that fully responds to the growing number of requests. Approximately 1,350 medical records have been opened from 2010 to December 2021. The most frequent presenting diagnoses included anxiety disorders (36.8%), severe stress and maladaptation syndromes (35.5%), and depressive episodes (18%). The outpatient clinic has proved to be a model with great impact on users offering a range of diagnostic and therapeutic offers responding to the requests of the community.

Hospitalized Patients with Medically Unexplained Physical Symptoms: Clinical Context and Economic Costs of Healthcare Management.

Medically Unexplained Physical Symptoms (MUPS) are physical symptoms without a medical explanation. This study collected data from hospitalized patients presenting MUPS, aiming to draw a clinical and socio-demographic profile of patients with MUPS, to explore psychopathological correlations of Somatic Symptoms Disorder (SSD) diagnosis, and to estimate economic costs related to hospital management for MUPS. The cross-sectional study consisted in the evaluation of data referring to hospitalized patients admitted between 2008 and 2018 in a teaching hospital in Northern Italy. A total of 273 patients presenting MUPS have been hospitalized. The sample showed a prevalence of female, married and employed patients. The most frequent wards involved are Neurology, Internal Medicine and Short Unit Stay. The most common symptoms found are headache, pain, syncope and vertigo. There is no evidence that a history of medical disease is associated with a diagnosis of SSD. A personality disorder diagnosis in patients with MUPS was associated with increased probability of having a diagnosis of SSD. A marginally significant positive association emerged with anxiety disorders, but not with depressive disorder. The overall estimated cost of hospitalization for patients with MUPS is 475'409.73 €. The study provides the investigation of a large number of patients with MUPS and a financial estimate of related hospitalization costs.

A straightforward multiparametric quality control protocol for proton magnetic resonance spectroscopy: Validation and comparison of various 1.5 T and 3 T clinical scanner systems.

PURPOSE: The aim of this study was to propose and validate across various clinical scanner systems a straightforward multiparametric quality assurance procedure for proton magnetic resonance spectroscopy (MRS). METHODS: Eighteen clinical 1.5 T and 3 T scanner systems for MRS, from 16 centres and 3 different manufacturers, were enrolled in the study. A standard spherical water phantom was employed by all centres. The acquisition protocol included 3 sets of single (isotropic) voxel (size 20 mm) PRESS acquisitions with unsuppressed water signal and acquisition voxel position at isocenter as well as off-center, repeated 4/5 times within approximately 2 months. Water peak linewidth (LW) and area under the water peak (AP) were estimated. RESULTS: LW values [mean (standard deviation)] were 1.4 (1.0) Hz and 0.8 (0.3) Hz for 3 T and 1.5 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficient of variation of LW and AP for different spatial positions of acquisition voxel were 43% (20%) and 11% (11%), respectively. The mean (standard deviation) phantom T2values were 1145 (50) ms and 1010 (95) ms for 1.5 T and 3 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficients of variation for repeated measurements of LW, AP and T2 were 25% (20%), 10% (14%) and 5% (2%), respectively. CONCLUSIONS: We proposed a straightforward multiparametric and not time consuming quality control protocol for MRS, which can be included in routine and periodic quality assurance procedures. The protocol has been validated and proven to be feasible in a multicentre comparison study of a fairly large number of clinical 1.5 T and 3 T scanner systems.

Neural correlates of lower limbs proprioception: An fMRI study of foot position matching.

Little is known about the neural correlates of lower limbs position sense, despite the impact that proprioceptive deficits have on everyday life activities, such as posture and gait control. We used fMRI to investigate in 30 healthy right-handed and right-footed subjects the regional distribution of brain activity during position matching tasks performed with the right dominant and the left nondominant foot. Along with the brain activation, we assessed the performance during both ipsilateral and contralateral matching tasks. Subjects had lower errors when matching was performed by the left nondominant foot. The fMRI analysis suggested that the significant regions responsible for position sense are in the right parietal and frontal cortex, providing a first characterization of the neural correlates of foot position matching.

Interplay between spinal cord and cerebral cortex metabolism in amyotrophic lateral sclerosis.

We recently reported the potential of Hough transform in delineating spinal cord metabolism by 18F-fluorodeoxyglucose PET/CT scanning in amyotrophic lateral sclerosis. The present study aimed to verify the relationship between spinal cord and brain metabolism in 44 prospectively recruited patients affected by amyotrophic lateral sclerosis submitted to 18F-fluorodeoxyglucose brain and whole-body PET/CT. Patients were studied to highlight the presence of brain hypo- or hypermetabolism with respect to healthy controls, and multiple regression analysis was performed to evaluate the correlation between spinal cord and brain metabolism. Our results confirmed higher 18F-fluorodeoxyglucose uptake in both cervical and dorsal spinal cord in patients with amyotrophic lateral sclerosis with respect to controls. This finding was paralleled by the opposite pattern in the brain cortex that showed a generalized reduction in tracer uptake. This hypometabolism was particularly evident in wide regions of the frontal-dorsolateral cortex while it did not involve the midbrain. Bulbar and spinal disease onset was associated with similar degree of metabolic activation in the spinal cord. However, among spinal onset patients, upper limb presentation was associated with a more pronounced metabolic activation of cervical segment. Obtained data suggest a differential neuro-pathological state or temporal sequence in disease progression.

Composite MRI measures and short-term disability in patients with clinically isolated syndrome suggestive of MS.

BACKGROUND: The use of composite magnetic resonance imaging (MRI) measures has been suggested to better explain disability in patients with multiple sclerosis (MS). However, little is known about the utility of composite scores at the earliest stages of the disease. OBJECTIVE: To investigate whether, in patients with clinically isolated syndrome (CIS), a composite MRI measure, rather than the single metrics, would explain conversion to MS and would better correlate with disability at baseline and at 1 year of follow-up. METHODS: Corticospinal tract (CST), corpus callosum (CC) and optic radiation (OR) volume, fractional anisotropy (FA), and mean diffusivity (MD) values were measured in 27 CIS patients and 24 healthy controls (HCs). Z-scores of FA, MD, and tract volume measures were calculated in patients, based on the corresponding measures obtained from HCs, and then combined in a composite score for each tract. Correlations between Z-scores at baseline and both the Expanded Disability Status Scale (EDSS) at baseline and at follow-up (FU-EDSS) were investigated. RESULTS: Only CST, CC, and OR composite scores as well as the CST volume were significantly associated with FU-EDSS ( p = 0.005, p = 0.007, p = 0.020, and p = 0.010, respectively). CONCLUSION: The combination of MRI measures rather than the individual metrics better captured the association between tissue damage in both the CC, OR and CST and short-term follow-up disability.

Functional Activation of Osteoclast Commitment in Chronic Lymphocytic Leukaemia: a Possible Role for RANK/RANKL Pathway.

Skeletal erosion has been found to represent an independent prognostic indicator in patients with advanced stages of chronic lymphocytic leukaemia (CLL). Whether this phenomenon also occurs in early CLL phases and its underlying mechanisms have yet to be fully elucidated. In this study, we prospectively enrolled 36 consecutive treatment-naïve patients to analyse skeletal structure and bone marrow distribution using a computational approach to PET/CT images. This evaluation was combined with the analysis of RANK/RANKL loop activation in the leukemic clone, given recent reports on its role in CLL progression. Bone erosion was particularly evident in long bone shafts, progressively increased from Binet stage A to Binet stage C, and was correlated with both local expansion of metabolically active bone marrow documented by FDG uptake and with the number of RANKL + cells present in the circulating blood. In immune-deficient NOD/Shi-scid, γcnull (NSG) mice, administration of CLL cells caused an appreciable compact bone erosion that was prevented by Denosumab. CLL cell proliferation in vitro correlated with RANK expression and was impaired by Denosumab-mediated disruption of the RANK/RANKL loop. This study suggests an interaction between CLL cells and stromal elements able to simultaneously impair bone structure and increase proliferating potential of leukemic clone.

Cost and morbidity analysis of chest port insertion in adults: Outpatient clinic versus operating room placement.

BACKGROUND: Totally implantable venous access devices (TIVADs) represent a convenient way for the administration of medications or nutrients. Traditionally, chest ports have been positioned by surgeons in the operating room, however there has been a transition over the years to port insertion by interventional radiologists in the radiology suite. The optimal method for chest port placement is still under debate. MATERIALS AND METHODS: Data on all adult patients undergoing isolated chest port placement at our institution in a 12-year period were retrospectively reviewed. The aim of this cohort study was to compare cost and morbidity for chest port insertion in two different settings: outpatient clinic and operating room. RESULTS: Between 2003 and 2015 a total of 527 chest ports were placed in adult patients. Of them, 262 procedures were performed in the operating room and 265 procedures were undertaken in the outpatient clinic. Patient characteristics were similar and there was no significant difference in early (<30 days, p = 0.54) and late complications (30-120 days, p = 0.53). The average charge for placement of a chest port was 1270 Euros in the operating room versus 620 Euros in the outpatient clinic. CONCLUSION: Our results suggest that chest ports can be safely placed in most patients under local anesthesia in the office setting without fluoroscopy or ultrasound guidance. Future randomized controlled studies may evaluate if surgeons or interventional radiologists should routinely perform these procedures in a dedicated office setting and reserve more sophisticated facilities only for patients at high risk of technical failure.

Structure and evolution of the mitochondrial control region of the pollen beetle Meligethes thalassophilus (Coleoptera: Nitidulidae).

The organization of the mitochondrial DNA (mtDNA) control region (CR) of the pollen beetle Meligethes thalassophilus is described. This mtDNA CR represents the longest sequenced for beetles so far, since the entire nucleotide sequence ranges from approximately 5000 to approximately 5500 bp. The CR of M. thalassophilus is organized in three distinct domains: a conserved domain near the tRNAIle gene, a variable domain flanking the 12S rRNA gene, and a relatively large central tandem array made up of a variable number of approximately 170 bp repeats that is responsible for the intraspecific length variation observed. Like other CRs found in insects, the M. thalassophilus CR contains two long homopolymeric runs that may be involved in mtDNA replication. Furthermore, conserved stem-and-loop structures in the repetitive domain were identified and their possible role in generating length variation is examined. Intraspecific comparison of the tandem repeat elements of M. thalassophilus suggests mechanisms of concerted evolution leading to homogenization of the repetitive region. The utility of such an array of tandem repeats as a genetic marker for assessing population-level variability and evolutionary relationships among populations is discussed. Finally, the technical difficulties found in isolating the mtDNA CR in beetles are remarked upon.

Differential screening of phage-ab libraries by oligonucleotide microarray technology.

A novel and efficient tagArray technology was developed that allows rapid identification of antibodies which bind to receptors with a specific expression profile, in the absence of biological information. This method is based on the cloning of a specific, short nucleotide sequence (tag) in the phagemid coding for each phage-displayed antibody fragment (phage-Ab) present in a library. In order to set up and validate the method we identified about 10,000 different phage-Abs binding to receptors expressed in their native form on the cell surface (10 k Membranome collection) and tagged each individual phage-Ab. The frequency of each phage-Ab in a given population can at this point be inferred by measuring the frequency of its associated tag sequence through standard DNA hybridization methods. Using tiny amounts of biological samples we identified phage-Abs binding to receptors preferentially expressed on primary tumor cells rather than on cells obtained from matched normal tissues. These antibodies inhibited cell proliferation in vitro and tumor development in vivo, thus representing therapeutic lead candidates.

Mouse spermine oxidase gene splice variants. Nuclear subcellular localization of a novel active isoform.

Spermine oxidase (SMO) is a flavoenzyme involved in polyamine homeostasis in animal cells. The mouse spermine oxidase gene (mSMO) codes for splice variants, including the previously reported major active isoform, herein named alfa (alpha). In the present work, eight additional gene splicing variants were characterized. The heterologous expression and biochemical characterization of three recombinant isoforms (namely mSMOmu, -gamma and -delta) revealed that only the recombinant protein mSMO micro displays biochemical characteristics similar to those of mSMOalpha; the other two recombinant proteins contained no detectable SMO activity. In order to investigate in greater detail, the SMO enzyme activity associated with their subcellular localization, mSMOalpha and -mu V5-tagged proteins were transiently and stably transfected in the murine neuroblastoma cell line, N18TG2. Very interestingly, the novel active mSMOmu isoform was found to be present in both nuclear and cytoplasmic compartments, thus providing the first evidence of SMO activity in the nucleus, while a cytoplasmic localization was confirmed for the mSMOalpha isoform. In addition, the relative transcription levels of the gene splicing variants were evaluated by RT-PCR analysis to verify a relationship with the SMO enzyme activity in various murine organs.

Structural and sequence evolution of U17 small nucleolar RNA (snoRNA) and its phylogenetic congruence in chelonians.

Vertebrate U17 RNA is an intron-encoded H/CA box containing snoRNA, which has been intensively studied in the last decade, though its precise role in ribosome biogenesis is not yet clear. A consensus secondary structure for the U17 RNA molecule has been derived from the comparative sequence and structural evolution analysis of U17 snoRNA among vertebrates. Its phylogenetic congruence above class level has been tested and preliminary data on chelonians suggest that also in this order, U17 snoRNA evolved congruently with phylogeny. We herein extend our analysis to other components of this reptile group. According to the sequence data that have also emerged from chelonians, the U17 RNA molecule can be divided into two main domains: the 5'-variable domain, which presents the sequence motifs capable of base-pairing with the 18S rRNA target and spanning STEM1, -2, and -3, and the 3'-conserved domain, consisting of STEM4. In vertebrates, the latter RNA region shows a high conservation both in secondary structure and in the presence of the three sequence motifs 5'-AUUCCUA-3', 5'-U(G/U)ACU-3', and 5'-AACCC-3'. We tested the phylogenetic congruence of U17 evolution with chelonian relationships: Our results are significantly similar to those emerging from mtDNA and morphological systematics. Some discrepancies (e.g., the position of Platysternon) need to be addressed in greater depth.