High-pressure homogenization and high hydrostatic pressure processing of human milk: Preservation of immunological components for human milk banks.

Human milk (HM) constitutes the first immunological barrier and the main source of nutrients and bioactive components for newborns. Immune factors comprise up to 10% of the protein content in HM, where antibodies are the major components (mainly IgA, IgG, and IgM). In addition, antibacterial enzymes such as lysozyme and immunoregulatory factors such as soluble cluster of differentiation 14 (sCD14) and transforming growth factor ß2 (TGF-ß2) are also present and play important roles in the protection of the infant's health. Donor milk processed in HM banks by Holder pasteurization (HoP; 62.5°C, 30 min) is a safe and valuable resource for preterm newborns that are hospitalized, but is reduced in major immunological components due to thermal inactivation. We hypothesized that high hydrostatic pressure (HHP) and high-pressure homogenization (HPH) are 2 processes that can be used on HM to reduce total bacteria counts while retaining immunological components. We studied the effects of HHP (400, 450, and 500 MPa for 5 min applied at 20°C) and HPH (200, 250, and 300 MPa, milk inlet temperature of 20°C) applied to mature HM, on microbiological and immunological markers (IgA, IgG, IgM, sCD14, and TGF-ß2), and compared them with those of traditional HoP in HM samples from healthy donors. The HHP processing between 400 and 500 MPa at 20°C reduced counts of coliform and total aerobic bacteria to undetectable levels (<1.0 log cfu/mL) while achieving approximately 100% of immunological component retention. In particular, comparing median percentages of retention of immunological components for 450 MPa versus HoP, we found 101.5 versus 50.5% for IgA, 89.5 versus 26.0% for IgM, 104.5 versus 75.5% for IgG, 125.0 versus 72.5% for lysozyme, 50.6 versus 0.1% for sCD14, and 88.5 versus 61.1% for TGF-ß2, respectively. Regarding HPH processing, at a pressure of 250 MPa and inlet temperature of 20°C, the process showed good potential to reduce coliforms to undetectable levels and total aerobic bacteria to levels slightly above those obtained by HoP. The median percentages of retention of immunological markers for HPH versus HoP were 71.5 versus 52.0%, 71.0 versus 27.0%, 104.0 versus 66.5%, and 30.9 versus 0.2%, for IgA, IgM, IgG, and sCD14, respectively; results did not significantly differ for lysozyme and TGF-ß2. The HPH at 300 MPa produced higher inactivation of immunological components, similar to values achieved with HoP.

Combined effect of genetic variants in the GluN2B coding gene (GRIN2B) on prefrontal function during working memory performance.

BACKGROUND: The GluN2B subunit of N-methyl-d-aspartate receptors is crucially involved in the physiology of the prefrontal cortex during working memory (WM). Consistently, genetic variants in the GluN2B coding gene (GRIN2B) have been associated with cognitive phenotypes. However, it is unclear how GRIN2B genetic variation affects gene expression and prefrontal cognitive processing. Using a composite score, we tested the combined effect of GRIN2B variants on prefrontal activity during WM performance in healthy subjects. METHOD: We computed a composite score to combine the effects of single nucleotide polymorphisms on post-mortem prefrontal GRIN2B mRNA expression. We then computed the composite score in independent samples of healthy participants in a peripheral blood expression study (n = 46), in a WM behavioural study (n = 116) and in a WM functional magnetic resonance imaging study (n = 122). RESULTS: Five polymorphisms were associated with GRIN2B expression: rs2160517, rs219931, rs11055792, rs17833967 and rs12814951 (all corrected p < 0.05). The score computed to account for their combined effect reliably indexed gene expression. GRIN2B composite score correlated negatively with intelligence quotient, WM behavioural efficiency and dorsolateral prefrontal cortex activity. Moreover, there was a non-linear association between GRIN2B genetic score and prefrontal activity, i.e. both high and low putative genetic score levels were associated with high blood oxygen level-dependent signals in the prefrontal cortex. CONCLUSIONS: Multiple genetic variants in GRIN2B are jointly associated with gene expression, prefrontal function and behaviour during WM. These results support the role of GRIN2B genetic variants in WM prefrontal activity in human adults.

Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli.

BACKGROUND: Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing. METHOD: A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence. RESULTS: We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing. CONCLUSIONS: Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.

Evidence that hippocampal-parahippocampal dysfunction is related to genetic risk for schizophrenia.

BACKGROUND: Abnormalities in hippocampal-parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state. METHOD: We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects. RESULTS: Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects. CONCLUSIONS: Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.

Load-dependent dysfunction of the putamen during attentional processing in patients with clinically isolated syndrome suggestive of multiple sclerosis.

BACKGROUND: Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. OBJECTIVES: The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. METHODS: Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. RESULTS: CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. CONCLUSIONS: This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.

Catechol-O-methyltransferase Val(158)Met association with parahippocampal physiology during memory encoding in schizophrenia.

BACKGROUND: Catechol-O-methyltransferase (COMT) Val158Met has been associated with activity of the mesial temporal lobe during episodic memory and it may weakly increase risk for schizophrenia. However, how this variant affects parahippocampal and hippocampal physiology when dopamine transmission is perturbed is unclear. The aim of the present study was to compare the effects of the COMT Val158Met genotype on parahippocampal and hippocampal physiology during encoding of recognition memory in patients with schizophrenia and in healthy subjects. METHOD: Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we studied 28 patients with schizophrenia and 33 healthy subjects matched for a series of sociodemographic and genetic variables while they performed a recognition memory task. RESULTS: We found that healthy subjects had greater parahippocampal and hippocampal activity during memory encoding compared to patients with schizophrenia. We also found different activity of the parahippocampal region between healthy subjects and patients with schizophrenia as a function of the COMT genotype, in that the predicted COMT Met allele dose effect had an opposite direction in controls and patients. CONCLUSIONS: Our results demonstrate a COMT Val158Met genotype by diagnosis interaction in parahippocampal activity during memory encoding and may suggest that modulation of dopamine signaling interacts with other disease-related processes in determining the phenotype of parahippocampal physiology in schizophrenia.

Iatrogenic benign paroxysmal positional vertigo: review and personal experience in dental and maxillo-facial surgery.

The post-traumatic origin of benign paroxysmal positional vertigo remains the most likely, from a patho-physiologic point of view. Benign paroxysmal positional vertigo due to surgical "traumas" has been described in the medical literature. According to personal experience, these iatrogenic cases represent a rare possibility and may be the consequence of surgical interventions differing according to the anatomical district involved and surgical technique performed. The temporal relationship with the surgical action and clinical features may be involved in some of these cases, even if it is not possible to define any real cause-effect link. Herewith some cases of paroxysmal positional vertigo are described, strongly held to be of iatrogenic origin, focusing on dental and maxillo-facial surgery as risk factors for benign paroxysmal positional vertigo.

Interaction between DRD2 variation and sound environment on mood and emotion-related brain activity.

Sounds, like music and noise, are capable of reliably affecting individuals' mood and emotions. However, these effects are highly variable across individuals. A putative source of variability is genetic background. Here we explored the interaction between a functional polymorphism of the dopamine D2 receptor gene (DRD2 rs1076560, G>T, previously associated with the relative expression of D2S/L isoforms) and sound environment on mood and emotion-related brain activity. Thirty-eight healthy subjects were genotyped for DRD2 rs1076560 (G/G=26; G/T=12) and underwent functional magnetic resonance imaging (fMRI) during performance of an implicit emotion-processing task while listening to music or noise. Individual variation in mood induction was assessed before and after the task. Results showed mood improvement after music exposure in DRD2GG subjects and mood deterioration after noise exposure in GT subjects. Moreover, the music, as opposed to noise environment, decreased the striatal activity of GT subjects as well as the prefrontal activity of GG subjects while processing emotional faces. These findings suggest that genetic variability of dopamine receptors affects sound environment modulations of mood and emotion processing.

DRD2 co-expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia.

Genetic risk for schizophrenia (SCZ) is determined by many genetic loci whose compound biological effects are difficult to determine. We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene DRD2 co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expression pathway enriched for SCZ risk genes. Next, we identified non-coding single-nucleotide polymorphisms (SNPs) associated with co-expression of this pathway. These SNPs were associated with regulatory genetic loci in the dorsolateral prefrontal cortex (P<0.05). We summarized their compound effect on co-expression into a Polygenic Co-expression Index (PCI), which predicted DRD2 pathway co-expression in both mRNA data sets (all P<0.05). We associated the PCI with brain activity during WM performance in two independent samples of healthy individuals (total N=368) and 29 patients with SCZ who performed the n-back task. Greater predicted DRD2 pathway prefrontal co-expression was associated with greater prefrontal activity and longer WM reaction times (all corrected P<0.05), thus indicating inefficient WM processing. Blind prediction of treatment response to antipsychotics in two independent samples of patients with SCZ suggested better clinical course of patientswith greater PCI (total N=87; P<0.05). The findings on this DRD2 co-expression pathway are a proof of concept that gene co-expression can parse SCZ risk genes into biological pathways associated with intermediate phenotypes as well as with clinically meaningful information.

Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders.

Exposure to early-life stress (ELS) may heighten the risk for psychopathology at adulthood. Here, in order to identify common genes that may keep the memory of ELS through changes in their methylation status, we intersected methylome analyses performed in different tissues and time points in rats, non-human primates and humans, all characterized by ELS. We identified Ankyrin-3 (Ank3), a scaffolding protein with a strong genetic association for psychiatric disorders, as a gene persistently affected by stress exposure. In rats, Ank3 methylation and mRNA changes displayed a specific temporal profile during the postnatal development. Moreover, exposure to prenatal stress altered the interaction of ankyrin-G, the protein encoded by Ank3 enriched in the post-synaptic compartment, with PSD95. Notably, to model in humans a gene by early stress interplay on brain phenotypes during cognitive performance, we demonstrated an interaction between functional variation in Ank3 gene and obstetric complications on working memory in healthy adult subjects. Our data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders.

Cell adhesion molecules in cord blood hematopoietic progenitors.

We investigated the expression of different cell adhesion molecules on cord blood (CB) and bone marrow (BM) CD34+/CD38+ and CD34+/CD38- cells. CD11a and CD62L were more expressed in CB than in BM CD34+/CD38- subset, suggesting a possible advantage in homing and engraftment. A short exposure to various cytokines increased CD62L expression only in the more differentiated CB and BM CD34+/CD38+ cells.

Head and neck carcinoma with distant metastases: a retrospective analysis of 44 cases treated with cisplatin-based chemotherapeutic regimens.

The rarity of medical reports on the chemotherapeutic management of head and neck cancer metastatic to distant organs prompted us to review the effect of cisplatin-based regimens in this clinical setting. Out of 44 eligible patients, 10 patients (23%) achieved a CR, 16 patients (36%) has a PR, 7 (16%) no change, and 11 (25%) progressed. Patients with rhinopharyngeal carcinoma showed a 69% overall response rate, while those with other head and neck carcinomas had a 54% overall response rate. No preferential site of response was detected. The difference in mean survival of responding patients between the rhinopharyngeal group and the non-rhinopharyngeal group was statistically significant (P < 0.05). Responding patients survived longer than non responders (P < 0.05 in both groups). Interestingly, 3 patients in the rhinopharyngeal cancer group survived more than 2 years from the start of chemotherapy for metastatic disease. These data strengthen the observation that rhinopharyngeal carcinoma, even with distant metastases, responds to chemotherapy better than other carcinomas arising in the head and neck region. Moreover, although survival is still dismal, cisplatin-based systemic chemotherapy seems an effective palliative treatment for metastatic head and neck cancer.

Long-term follow-up of treated dental phobics.

Behavioural treatment programmes have been shown repeatedly to be effective in alleviating dental anxiety but few studies have provided long-term follow-ups. In this study, dentally anxious Ss who had completed a 4-session behavioural group programme were followed up for periods between 1 and 4 years after successful completion of treatment. It was hypothesized that dental visit satisfaction would be associated with regular dental attendance. 88% of Ss contacted agreed to cooperate; of these, 70% were still maintaining regular check-ups. There were no differences between regular and irregular attenders in terms of age, gender, education, marital status, degree of pre-treatment avoidance or time elapsed since completion of the programme. However, Ss who did not see their dentists regularly were more likely to have shown higher levels of anxiety immediately after completing the programme, less concordance between the subjective and overt behavioural aspects of anxiety and to have experienced more invasive than non-invasive procedures than the others. It was argued that dentally anxious individuals are not a homogeneous group and that a better understanding of their individual differences would lead to the development of more efficacious treatment procedures.

Malignancy in horseshoe kidneys: review and discussion of surgical implications.

OBJECTIVE: Horseshoe kidney is one of the most common congenital anomalies of renal structure. Not infrequently, surgical management of both benign and malignant disorders is required in patients with horseshoe kidney due to the susceptibility to certain conditions. The literature suggests a greater proclivity to certain renal tumors with this anomaly. We present three cases of malignancy in horseshoe kidneys. The unique technical challenges presented by these cases and the surgical approaches are discussed. METHODS: Three patients with tumors involving horseshoe kidneys are reviewed and their management discussed. RESULTS: Two patients were found to have renal cell carcinoma (RCC) and one had transitional carcinoma (TCC). Computed tomography (CT) and angiography were used in the work-up and preoperative planning of these cases. One patient with RCC received pre-operative renal artery embolization. Partial nephrectomy was performed in each patient with an aim at early vascular control of the tumors, identification of the collecting systems and ureters, as well as ensuring a 1 cm surgical margin. No patient required dialysis post-operatively. One patient died in the early post-operative period of a myocardial infarction; one patient developed brain metastases 18 months post-operatively, received palliative radiation and is alive 42 months after surgery; the other patient was free of disease for approximately 36 months but recently developed osseous metastases to her pelvis. CONCLUSIONS: Techniques developed for partial nephrectomy may be used in the treatment of tumors in horseshoe kidneys. Survival is related to the grade and stage of disease.

[Suppression of the opiate withdrawal syndrome with GABA analogs, low-dose psychotropic drugs and acupuncture]. / Soppressione della sindrome da astinenza da oppiacei con farmaci GABAergici, psicofarmaci a basso dosaggio e agopuntura.

15 male heroin addicts, 19-26 yr, were given 20 hospital treatments for detoxifying. Therapeutic program was based on GABAergic drugs (1-glutamine, sodium valproate, pyridoxine), low doses psychodrugs and acupuncture, added from the 3rd day. A full avoidance of the withdrawal syndrome was reached in 15 out of 18 Ss so treated with 8-10 hours following the last heroin injection, while the remaining 3 Ss experienced only a slight form of syndrome, which completely disappeared within the 24th hour. The 2 Ss manifesting evident symptoms of withdrawal and starting the therapeutic program respectively at the 20th and 32nd hour had their syndrome stopped and suppressed respectively within the 24th and 48th hour. Acupuncture accelerated the somatopsychic recovery leading to a lowering of the daily doses of the drugs used.

[Acupuncture as a part of a program of detoxification and weaning from opiates: 25 cases]. / Agopuntura come parte di un programma di disintossicazione e disassuefazione da oppiacei: 25 cases.

Presents results of a detoxification and habit loosing program carried out in 25 morphine-like substances addicts (mainly heroine) aged 19-26. The therapeutic treatment based on gabaergic drugs (l-glutamine, sodium valproate and piridoxine), low doses psychodrugs (tricyclics and benzodiacepines) and acupuncture, began in 13 subjects at the hospital and continued at the outpatients' service, while 12 subjects were treated only at the outpatients' service. Follow up: 6 subjects of the hospitalized group free from the addiction (5 subjects from more than 1 year after their discharge); 3 subjects of the outpatients' group abstinent from no more than 4 months after discharge. Biochemical mechanisms involved in this therapeutic program are extensively discussed.

[Influence of high environmental temperature on various parameters of blood coagulation in healthy subjects and in thrombosis risk patients]. / Influenza dell'elevata temperatura ambientale su alcuni parametri della coagulazione in soggetti sani ed in pazienti a rischio trombotico.

The effects of environmental hyperthermia (exposure to a hot, dry microclimate) on the human body were investigated with particular reference to certain clotting parameters in healthy subjects and patients at risk of thrombosis. The study covered 70 volunteers, 10 of them clinically healthy (6 males and 4 females) aged 37.7 +/- 9.7 and 60 patients at risk of thrombosis aged 18-60 and divided according to pathology as follows: 26 with ischaemic cardiopathy, 22 with metabolic disorders (12 diabetics, 8 with dyslipidaemia, 2 with hyperuricaemia) and 12 with obliterating arteriopathies of the lower extremities (Fontaine stage 2 and 3). The following standardised protocol was adopted: 2 hours exposure in a controlled climate chamber (40 degrees C, 40-50% humidity, standard air speed 4 m/min, barometric pressure 760 mmHg) for a total of 8 exposures (2 per week for 1 month). This approach was adopted in order to assess not only the effect of each single exposure but also the role of any adaptation to heat. Three blood samples were taken from each subject for each session: the first in basal conditions in a comfortable environment, the second at the end of the 2 hour exposure; the third 30 minutes after the end of the session. Simultaneously samples of arterial blood were taken for pH assays and a spleen echography was performed in basal conditions and at the end of the session for each subject. Each blood sample was tested for several parameters essentially attributable to blood concentration for a broader view of the biological effects of exposure to heart (Ht, blood protein, Nat, K+). The clotting factors under specific study were also assessed (platelet count and volume, beta-thromboglobulin, PF4, von Willebrand Factor VIII, thromboxane B2, fibronectin). Body weight, blood pressure and oral temperature were also measured in all subjects before and after each session. In all subjects both healthy and at risk of thrombosis oral temperature increased (1 +/- 0.4 degrees); on average blood pressure was already higher in basal conditions in the patient group; body weight fell by 900 +/- 120 G in both groups. Ht and blood protein increased significantly in both groups while electrolyte changes were insignificant and blood pH showed a tendency towards acidosis. Clotting parameters revealed a tendency towards thrombophilia in all subjects: platelet count and volume were already higher in the patient group in basal conditions and increased after exposure to hyperthermia. Beta-thromboglobulin, FP4, Factor VIII, thromboxane B2 and fibronectin all increased.(ABSTRACT TRUNCATED AT 400 WORDS)

Tell me a story: the therapeutic metaphor in the practice of pediatric occupational therapy.

In the crafting of therapeutic intervention, pediatric occupational therapists are challenged to provide therapeutic modalities that are as stimulating and imaginative as the child's world, while offering appropriate and meaningful solutions to the child's problems. Storytelling, coupled with the visual, auditory, and kinesthetic stimulation of guided affective imagery, offers a stimulating treatment approach for both the child or adolescent and the occupational therapist. This paper provides an overview of the use of storytelling, metaphorical forms and expressions, and guided affective imagery in occupational therapy with children.

Free D-aspartate regulates neuronal dendritic morphology, synaptic plasticity, gray matter volume and brain activity in mammals.

D-aspartate (D-Asp) is an atypical amino acid, which is especially abundant in the developing mammalian brain, and can bind to and activate N-methyl-D-Aspartate receptors (NMDARs). In line with its pharmacological features, we find that mice chronically treated with D-Asp show enhanced NMDAR-mediated miniature excitatory postsynaptic currents and basal cerebral blood volume in fronto-hippocampal areas. In addition, we show that both chronic administration of D-Asp and deletion of the gene coding for the catabolic enzyme D-aspartate oxidase (DDO) trigger plastic modifications of neuronal cytoarchitecture in the prefrontal cortex and CA1 subfield of the hippocampus and promote a cytochalasin D-sensitive form of synaptic plasticity in adult mouse brains. To translate these findings in humans and consistent with the experiments using Ddo gene targeting in animals, we performed a hierarchical stepwise translational genetic approach. Specifically, we investigated the association of variation in the gene coding for DDO with complex human prefrontal phenotypes. We demonstrate that genetic variation predicting reduced expression of DDO in postmortem human prefrontal cortex is mapped on greater prefrontal gray matter and activity during working memory as measured with MRI. In conclusion our results identify novel NMDAR-dependent effects of D-Asp on plasticity and physiology in rodents, which also map to prefrontal phenotypes in humans.

Gadd45α activity is the principal effector of Shigella mitochondria-dependent epithelial cell death in vitro and ex vivo.

Modulation of death is a pathogen strategy to establish residence and promote survival in host cells and tissues. Shigella spp. are human pathogens that invade colonic mucosa, where they provoke lesions caused by their ability to manipulate the host cell responses. Shigella spp. induce various types of cell death in different cell populations. However, they are equally able to protect host cells from death. Here, we have investigated on the molecular mechanisms and cell effectors governing the balance between survival and death in epithelial cells infected with Shigella. To explore these aspects, we have exploited both, the HeLa cell invasion assay and a novel ex vivo human colon organ culture model of infection that mimics natural conditions of shigellosis. Our results definitely show that Shigella induces a rapid intrinsic apoptosis of infected cells, via mitochondrial depolarization and the ensuing caspase-9 activation. Moreover, for the first time we identify the eukaryotic stress-response factor growth arrest and DNA damage 45α as a key player in the induction of the apoptotic process elicited by Shigella in epithelial cells, revealing an unexplored role of this molecule in the course of infections sustained by invasive pathogens.