Advanced molecular approaches in male infertility diagnosis†.

In the recent years a special attention has been given to a major health concern namely to male infertility, defined as the inability to conceive after 12 months of regular unprotected sexual intercourse, taken into account the statistics that highlight that sperm counts have dropped by 50-60% in recent decades. According to the WHO, infertility affects approximately 9% of couples globally, and the male factor is believed to be present in roughly 50% of cases, with exclusive responsibility in 30%. The aim of this article is to present an evidence-based approach for diagnosing male infertility that includes finding new solutions for diagnosis and critical outcomes, retrieving up-to-date studies and existing guidelines. The diverse factors that induce male infertility generated in a vast amount of data that needed to be analyzed by a clinician before a decision could be made for each individual. Modern medicine faces numerous obstacles as a result of the massive amount of data generated by the molecular biology discipline. To address complex clinical problems, vast data must be collected, analyzed, and used, which can be very challenging. The use of artificial intelligence (AI) methods to create a decision support system can help predict the diagnosis and guide treatment for infertile men, based on analysis of different data as environmental and lifestyle, clinical (sperm count, morphology, hormone testing, karyotype, etc.), and "omics" bigdata. Ultimately, the development of AI algorithms will assist clinicians in formulating diagnosis, making treatment decisions, and predicting outcomes for assisted reproduction techniques.

NGS and phenotypic ontology-based approaches increase the diagnostic yield in syndromic retinal diseases.

Syndromic retinal diseases (SRDs) are a group of complex inherited systemic disorders, with challenging molecular underpinnings and clinical management. Our main goal is to improve clinical and molecular SRDs diagnosis, by applying a structured phenotypic ontology and next-generation sequencing (NGS)-based pipelines. A prospective and retrospective cohort study was performed on 100 probands with an a priori diagnosis of non-Usher SRDs, using available clinical data, including Human Phenotype Ontology annotation, and further classification into seven clinical categories (ciliopathies, specific syndromes and five others). Retrospective molecular diagnosis was assessed using different molecular and bioinformatic methods depending on availability. Subsequently, uncharacterized probands were prospectively screened using other NGS approaches to extend the number of analyzed genes. After phenotypic classification, ciliopathies were the most common SRD (35%). A global characterization rate of 52% was obtained, with six cases incompletely characterized for a gene that partially explained the phenotype. An improved characterization rate was achieved addressing prospective cases (83%) and well-recognizable syndrome (62%) subgroups. The 27% of the fully characterized cases were reclassified into a different clinical category after identification of the disease-causing gene. Clinical-exome sequencing is the most appropriate first-tier approach for prospective cases, whereas whole-exome sequencing and bioinformatic reanalysis increases the diagnosis of uncharacterized retrospective cases to 45%, mostly those with unspecific symptoms. Our study describes a comprehensive approach to SRDs in daily clinical practice and the importance of thorough clinical assessment and selection of the most appropriate molecular test to be used to solve these complex cases and elucidate novel associations.

Why not the best? Social anxiety symptoms and perfectionism among Israeli Jews and Arabs: a comparative Study.

BACKGROUND: Social Anxiety Disorder (SAD) has been repeatedly shown to be very prevalent in the Western society and is characterized by low self-esteem, pessimism, procrastination and also perfectionism. Very few studies on SAD have been done in the Middle East or in Arab countries, and no study tackled the relationship between social anxiety symptoms and perfectionism in non-Western samples. METHODS: We examined social anxiety symptoms and perfectionism in a group of 132 Israeli Jewish (IJ) and Israeli Arab (IA) students. Subjects completed the Liebowitz Social Anxiety Scale (LSAS), the Multidimensional Perfectionism Scale (MPS), the Negative Automatic Thoughts Questionnaire (ATQ-N), the Positive Automatic Thoughts Questionnaire (ATQ-P) and a socio-demographic questionnaire. RESULTS: The rate of SAD in our sample according to a LSAS score of 60 or more was 17.2% (IJ=13.8%, IA=19%, ns). The correlation between perfectionism and the LSAS was high in both groups, and in particular in the IJ group. The IA group had higher scores of social avoidance, of ATQ-P and of two of the MPS subscales: parental expectations and parental criticism. Concern over mistakes and negative automatic thoughts positively predicted social fear in the IJ group, whereas in the IA group being female, religious and less educated positively predicted social fear. Negative automatic thoughts and age positively predicted social avoidance in the IJ group. In general, the IJ and IA subjects showed higher social anxiety, higher ATQ-N scores and lower parental expectations as compared with non-clinical US samples. CONCLUSIONS: Social anxiety symptoms and perfectionism are prevalent in Arab and Jewish students in Israel and seem to be closely related. Further studies among non-western minority groups may detect cultural influences on social anxiety and might add to the growing body of knowledge on this intriguing condition.

Epidemiology of obsessive-compulsive disorder: a world view.

The worldwide prevalence of obsessive-compulsive disorder (OCD) is approximately 2% of the general population. Symptoms of OCD include fear of contamination by dirt or germs; constant checking; repetitive, intrusive thoughts of a somatic, aggressive, or sexual nature; extreme slowness; and an inordinate concern with orderliness and symmetry. Differential diagnosis is sometimes complicated by the overlap between OCD and obsessive-compulsive personality disorder (OCPD). The most common complication of OCD is depression. However, while both serotonergic and nonserotonergic antidepressants are effective in treating patients with depression, only serotonergic medications are effective in treating OCD patients. Because OCD patients often attempt to conceal their symptoms, it is incumbent on clinicians to screen for OCD in every mental status examination, since appropriate treatment can often result in improved quality of life.

The Ganser syndrome in two adolescent brothers.

The Ganser syndrome is rare in children and adolescents. Two cases of Ganser syndrome in adolescent brothers, both of whom developed the syndrome while in jail and awaiting trial, are presented. Both brothers subsequently developed signs and symptoms indicative of affective disorder. The differential diagnosis and the management of these two patients are discussed in the light of the nosological controversies surrounding this clinical entity.

Seven-year follow-up of child survivors of a bus-train collision.

OBJECTIVE: To assess the long-term effects of a traumatic bus-train collision and to examine the effect of levels of exposure and immediate reactions on long-term adjustment. METHOD: Seven years after the accident, 389 subjects, all doing compulsory army service, filled out self-report questionnaires assessing symptoms of posttraumatic stress disorder (PTSD), psychiatric symptomatology, and military functioning. In addition, subjects were questioned about their immediate reactions to the traumatic event. RESULTS: The most highly exposed subjects reported the highest levels of somatization, depression, phobic anxiety, and psychoticism and more PTSD symptoms. Acute stress symptoms and manifestations of fear immediately after the accident were strongly related to long-term maladjustment CONCLUSIONS: The results suggest that the investigation and assessment of long-term adjustment after traumatic events should take into account both contextual factors, such as the level of exposure to the event, and personal factors, such as the victims' immediate reactions.

Fluvoxamine open-label treatment of adolescent inpatients with obsessive-compulsive disorder or depression.

OBJECTIVE: Fluvoxamine, a monocyclic, specific serotonin uptake inhibitor with demonstrated efficacy in obsessive-compulsive disorder (OCD) and depression in adults, is marketed in more than 30 countries worldwide, including Israel. In the United States, where fluvoxamine is available only on an investigational basis, marketing appears imminent. This study evaluates the safety and efficacy of fluvoxamine in adolescents. METHOD: In an 8-week, open-label trial of fluvoxamine, 20 adolescent inpatients, ages 13 to 18 years, were treated for OCD (n = 14) or major depressive disorder (MDD)(n = 6) with daily doses ranging from 100 to 300 mg. Target symptoms were rated at regular intervals with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS); Suicide Potential Scales (SPS); Beck Depression Inventory (BDI); the Overt Aggression Scale (OAS); and the Children's Global Adjustment Scale (CGAS). RESULTS: Fluvoxamine proved relatively safe and was especially effective in the patients with OCD; mean Y-BOCS scores decreased significantly (p < .0001) from 28.0 to 19.8 on medication. Although fluvoxamine also appeared effective in decreasing depression and bulimic symptoms, its impact on impulsive, suicidal, and anorectic symptoms was less clear. The commonest side effects (n > or = 3) were dermatitis, insomnia, hyperactivity, excitement, anxiety, tremor, and nausea. Fluvoxamine was discontinued in four patients because of side effects; the most serious side effect occurred in two debilitated anorexic patients, of whom one became delirious and the other developed hallucinations. CONCLUSION: Preliminary evidence suggests that short-term treatment of adolescents with fluvoxamine is relatively safe and may be effective for OCD and some affective spectrum symptoms.

Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.

OBJECTIVE: To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. METHOD: Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. RESULTS: Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. CONCLUSIONS: The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.

A double-blind crossover comparison of clomipramine and desipramine in the treatment of panic disorder.

OBJECTIVE: To compare the efficacy of clomipramine hydrochloride (CMI), a serotonin reuptake inhibitor with the noradrenergic tricyclic antidepressant agent, and desipramine hydrochloride (DMI) for patients with panic disorder (PD). METHOD: Following a 2-week, single-blind placebo washout phase, 17 PD outpatients completed a 16-week, double-blind, crossover comparison of CMI and DMI. Key outcome measures included panic attacks frequency, the NIMH Global Scales for Anxiety, Depression and Impairment, Hamilton Anxiety Scale (Psychic and Somatic Subscales), Zung Anxiety Inventory (Raw and Index Subscales) and the Spielberger State Anxiety Scale. RESULTS: Both CMI and DMI led to significant improvement from baseline placebo state in panic attacks frequency and behavioral ratings (p<0.001). CMI led to a greater reduction in the frequency of panic attacks (p=0.028) and was superior to DMI on ratings of anxiety: NIMH Global Anxiety, Zung Anxiety Scale (Raw and Index) and the Spielberger Anxiety Scale. No difference was found between the drugs on the NIMH Global Impairment Scale and the Hamilton Somatic and Psychic Scales. CONCLUSION: Both drugs appeared to have significant therapeutic effects in patients with PD, but CMI appeared to be more effective. The effectiveness of the serotonergic drug suggests that the role of the serotonergic system in the pathogenesis of PD should be further explored.

Emergence of kleptomania during treatment for depression with serotonin selective reuptake inhibitors.

Kleptomania, one of the rare impulse-control disorders, is characterized by an irresistible impulse to steal objects not needed for personal use or monetary value. There is a comorbidity between mood disorders, eating disorders, anxiety disorders, personality disorders, and kleptomania. Several recent case reports have suggested that serotonin reuptake inhibitors could be effective in the treatment of obsessive-compulsive spectrum disorders and specifically in kleptomania. We describe three depressed patients who paradoxically experienced kleptomanic behavior during treatment with serotonin selective reuptake inhibitors.

The pathogenesis and treatment of obsessive-compulsive disorder.

The outlook for patients with obsessive-compulsive disorder (OCD) began to change in the early 1980s with the introduction of clomipramine (CMI), a serotonergic antidepressant. The observation that only drugs with a serotonergic profile are effective in OCD has been the basis for the serotonergic hypothesis of OCD. The serotonin-selective reuptake inhibitors are effective alternatives for CMI and can be used when the patient cannot use or tolerate CMI. In this review, we examine the pathophysiology of OCD, based on drug response profile, peripheral markers of serotonergic function, pharmacologic challenge studies, and neuroimaging. We also consider the medications found to be effective in OCD, the length of treatment, with special regard for maintenance therapy, and such issues as the approach for the treatment-resistant patient, augmentation strategies, and nonpharmacological treatments.

Vitamin E treatment in tardive dystonia.

Tardive dystonia is a disorder characterized by abnormally sustained posturing associated with the use of dopamine-receptor blocking agents such as antipsychotic drugs. However, the structural pathologic and pathophysiologic features of this disorder are unknown, and no consistently effective pharmacologic treatment is available. Patients with tardive dystonia mostly are young men. We present the case of one substantially improved with treatment by 1200 mg/d (IU) of vitamin E.

Valproic acid in ultra-rapid cycling: a case report.

Valproic acid has been proven to be efficient in the treatment of bipolar affective disorders as an adjunctive agent to lithium and carbamazepine. Recently, its efficacy in rapid cycling states has attracted interest. We present the case of a male patient with bipolar affective disorder who developed an extreme state of ultra-rapid cycling (48-h cycles). Only the addition of valproic acid therapy to prior lithium treatment succeeded in curtailing the ultra-rapid cycling. Several issues regarding ultra-rapid cycling and valproate's efficacy in bipolar disorder are discussed.

Nightmares related to fluoxetine treatment.

Sleep disturbances are found in most depressive patients. Serotonin reuptake inhibitors, such as fluoxetine hydrochloride, seem to improve sleep by changing the depressive affect and the underlying biological mechanisms. Insomnia is an occasional adverse effect of the medication, but it was shown that only 2-3% of the patients with fluoxetine-induced insomnia discontinued the drug for this reason. We could not find any report of nightmares or night terrors under fluoxetine treatment. We report on four patients who experienced nightmares on fluoxetine monotherapy.

The treatment of kleptomania with serotonin reuptake inhibitors.

Kleptomania is characterized by an irresistible impulse to steal objects not needed for personal use or for their monetary value. Several recent case reports have shown that Serotonin Specific Reuptake Inhibitors (SSRIs) could be effective in the treatment of kleptomania just as it is in other obsessive-compulsive spectrum disorders. We report five cases of kleptomania patients who were successfully treated with fluoxetine or paroxetine in combination with a psychotherapeutic intervention. In one case, the discontinuation of the medication repeatedly led to the resurgence of the kleptomanic behavior. Our case series illustrates the effectiveness of SSRIs in kleptomania. It thus supports the assumption that this syndrome involves a dysfunctional serotoninergic mechanism.

A review of psychological debriefing after extreme stress.

Preventive intervention after exposure to traumatic events is a subject of increasing interest among mental health professionals. Psychological debriefing, which aims to reduce the risk of posttraumatic stress disorder and other psychopathological sequelae of traumatic experiences, is an example of such an intervention. The authors review the history of psychological debriefing and examine its efficacy. They conclude that psychological debriefing might be an effective intervention after extreme stress, although more support from controlled studies is required.

Combatting traffic accidents in the Israel Defence Forces: the role of the Medical Corps.

A combined plan of action of the Medical Corps in the battle against traffic accidents is described. The plan covers sound medical standards for military driver licensing, disqualification of drivers with medical problems, reporting of problematic drivers (epileptics and others) to the Israeli Ministry of Health, evaluating the driving fitness of drivers involved in traffic accidents, and finally, an education program for all Israel Defence Forces soldiers to be delivered by military physicians. Several medical aspects of traffic safety are highlighted. Scientific research and greater involvement of physicians and psychologists in this area is required if the trauma occurring daily on highways is to be eliminated and acute care hospital costs minimized.

Is caffeine involved in the pathogenesis of combat-stress reaction?

The role of caffeine in the pathogenesis of combat-stress reaction is discussed in light of the expanding literature on caffeine's influence on stress reactions in animals and in humans, and in regard to the two clinical entities concerning caffeine: caffeinism and caffeine withdrawal. It is proposed that caffeine is a contributing factor to the development of combat-stress reaction and that the use of decaffeinated coffee in military settings might reduce the prevalence of the various anxiety reactions, including combat-stress reaction.

A general hospital study of attempted suicide in adolescence: age and method of attempt.

Attempted suicide in adolescence is a major health problem and recent reports indicate a dramatic increase in the frequency of attempted and completed suicide among adolescents. The aim of this study was to evaluate the characteristics of adolescent admissions with attempted suicide in a large general hospital. The files of all children and adolescents admitted due to a suicide attempt between the years 1984 and 1994 were examined retrospectively, with regard to age, sex, method of attempt, season, year and length of hospitalization. Four hundred and four admissions with attempted suicide were recorded. The majority (83.7%) were females and drug overdose was the most common (92.8%) method used. Thirty patients (7.5%) repeated the attempt during the study period. No specific time of the year was associated with an increase in adolescent suicide attempt admissions. The most remarkable finding was that younger adolescents had a higher probability of performing a violent suicide attempt. Hypotheses for these trends are examined together with possible ramifications for treatment provision.

Cultural effects on eating attitudes in Israeli subpopulations and hospitalized anorectics.

We assessed eating attitudes and body image using the Eating Attitudes Test-26 (EAT: Garner & Garfinkel, 1979) and a 17-item body image scale in Israeli Jewish female high school populations in five distinct residential settings (kibbutz, moshav, city, and 2 different boarding schools); in five ethnically distinct Arab female high school populations (Muslim, Christian, Druze, Circassian, and Bedouin); and in a group of hospitalized adolescent girls with anorexia nervosa. We hypothesized that the attitudes of the adolescent females most exposed to Western body shape ideals and simultaneously undergoing role conflict between traditional and modern images of the female role would most resemble attitudes of anorectics. This was partly supported by the findings. Ethnic differences also emerged in attitude toward food. All the Arab populations except the Circassian showed strong Western influences in their attitudes toward eating and body image and thus may well be prone to epidemics of anorexia and similar eating disorders in the near future. Kibbutz girls were most similar to the anorectic group.