Despite the many changes occurring in the Western world from the

Despite the many changes occurring in the Western world from the 12th century onwards, this situation continued in India through the early part of the 19th century. In fact, various accounts of the late 17th century suggest that giving birth in India was no more hazardous than it was in England and that women were ‘quick in labour’ [13]. Public hospitals were established during Mughal period. Jahangir (son of Akbar) stated in his autobiography that on his accession to the throne, he ordered the establishment of hospitals in large cities at government expense [14]. Although the supply of local physicians was not

PLX-4720 purchase plentiful, the local physicians were able to deal with normal problems. As early as 1616, they knew the important characteristics of the bubonic plague and suggested suitable preventive measures [15]. The use of medicines had been fairly well developed among the Hindus, but dissection was considered to be irreligious. The Muslims, who did not have this restriction, performed a number of operations. As Elphinstone pointed out, “their surgery is as remarkable as their medicine, especially when we recollect their

ignorance www.selleckchem.com/products/KU-55933.html of anatomy. They cut for the kidney stone Libraries disease (Pathri), couched for the cataract, and extracted the foetus from the womb, and their early works enunciate no less than one hundred and twenty-seven surgical works” [16]. In the last

382 years, has there been a perceptible change in maternal health in India? While Mephenoxalone the country has grown by leaps and bounds, not much has changed in rural India so far as maternal health services are concerned. Health facilities can be state-of-the-art in urban areas, but in the villages, a host of challenges are present for a pregnant woman seeking proper maternal care and services. Poverty and illiteracy influence both expectations of and demand for quality services at health facilities. The sub-centres and the primary health centres are at the frontline for these women, yet they have failed to inspire confidence in health care delivery for a variety of reasons, not least the women’s blatant lack of decision-making power of their reproductive rights. For women who are the backbone of families, the much-touted ‘basic unit of society’, giving birth in the 21st century should be an occasion to celebrate new life, a manifestation of their special role to bear the next generation. Although Mumtaz was an empress and much loved by her besotted emperor, her powerlessness in reproductive choices was quite evident. Ordinary poor women would have the double burden of their gender constraints along with poverty and illiteracy impinging on health. A modern state cannot continue this injustice, which even an empress went through three centuries back.

(Mrs ) May Nwosu of the Department of Botany, University of Niger

(Mrs.) May Nwosu of the Department of Botany, University of Nigeria, Nsukka, Enugu State where the voucher specimens were deposited in the herbarium. A quantity (25 g) of powdered A. brasiliana leaves was weighed out and subjected to cold maceration in 125 ml of absolute ethanol for 24 h. The mixture was afterwards, filtered using Whatman No 1 filter paper. The filtrate was concentrated in an oven at 50 °C for 48 h and stored in a refrigerator at 4 °C until it was used. Six adult male Wistar rats

of between 7 and 12 weeks old with average weight of 120 ± 20 g were obtained from the Animal house of the Faculty high throughput screening assay of Veterinary Medicine, University of Nigeria, Nsukka. The animals were acclimatised for one week under a standard environmental condition with a 12 h light and dark cycle and maintained on a regular feed and water ad libitum. There was adherence to the Principles of Laboratory Animal Care. The Libraries Chemicals used for this study were of analytical grades and included: absolute ethanol (BDH Chemicals Ltd., Poole, England), ascorbic acid [standard anti-oxidant

(Sigma–Aldrich, Inc., St. Louis, USA)], glacial acetic acid (BDH Chemicals Ltd., Poole, England), thiobarbituric acid [TBA (BDH Chemicals Ltd., Poole, England)], trichloro acetic acid [TCA (BDH Chemicals Ltd., Poole, England)], carbon tetrachloride (BDH Chemicals Ltd., Poole, England), potassium chloride (BDH Chemicals Ltd., Poole, England), dipotassium hydrogen phosphate (BDH Chemicals whatever Ltd., Poole, England), phosphoric acid (BDH Chemicals Ltd., Poole, England), sulphanilamide (BDH Chemicals Selleckchem Vemurafenib Ltd., Poole, England), sodium nitroprusside (BDH Chemicals Ltd., Poole, England), potassium ferricyanide (BDH Chemicals Ltd., Poole, England), phosphate buffer (pH 7.4), ferrous sulphate heptahydrate (BDH Chemicals Ltd., Poole, England), ferric chloride (BDH Chemicals Ltd., Poole, England), 1,1-diphenyl-2-picrylhydrazyl (DPPH) reagent, [N-(1-naphthyl)-ethylene diamine] Griess reagent, normal saline and distilled water. The total phenolic content of the plant extract was determined by the method described by.8 The DPPH radical-scavenging activity

of the extract was determined by the method reported by.9 The ability of the ethanol extract of A. brasiliana to chelate Fe2+ was determined using a modified method of. 10 Nitric oxide radical-scavenging activity was performed as described by.11 The method reported by12 was used for this assay using 3 adult male Wistar rats. Carbon tetrachloride-induced lipid peroxidation test was performed using 3 adult male Wistar rats according to the method described by.13 The results were expressed as means of three replicates ± standard errors of the means (SEM). Linear regression plots were generated using Microsoft Excel for Windows 7. The concentration of total phenols as evaluated using the equation generated from the standard curve of total phenols was 0.031 ± 0.006 μg/ml of the extract.

C perfringens toxinotype B is the etiologic agent of dysentery i

C. perfringens toxinotype B is the etiologic agent of dysentery in newborn lambs and haemorrhagic enteritis and enterotoxemia in goats, calves and foals [2] and [3]. More recently, toxinotype B has been detected in a human with a clinical presentation of multiple sclerosis, providing clues for environment triggers of the disease [4]. C. perfringens toxinotype D affects mainly sheep and lambs but also causes infections in goats and calves [2] and [3]. The most important factor in initiating disease is the disruption of the microbial

balance in the gut due to overeating carbohydrate rich food, which causes proliferation of C. CB-839 mw perfringens and consequent overproduction of the toxin [2] and [5]. Overproduction of Etx causes increased intestinal permeability, facilitating entry of the toxin into the Libraries bloodstream and its spread into various organs, including the brain, lungs and kidneys. While infection of the central nervous system results in neurological disorders, the fatal effects on the organs often lead to sudden

death [6] and [7]. For full activity of the toxin, proteolytic processing is required, with carboxy-terminal and amino-terminal peptides removed. Toxin activation typically occurs in the gut either by digestive proteases Selleck Dorsomorphin of the host, such as trypsin and chymotrypsin [8], or by λ-protease produced by C. perfringens itself [9] and [10]. To prevent Etx-induced enterotoxemia in domesticated livestock, a number of commercial vaccines are available that have been used extensively over the past decades. These vaccines are based on either formaldehyde treated C. perfringens type D culture filtrate or formaldehyde-inactivated recombinant wild type toxin [11] and [12]. These vaccine preparations have several disadvantages: (1) complete removal of free formaldehyde is required to avoid possible toxic side effects, (2) toxoiding using formaldehyde can

show considerable batch to batch variation in immunogenicity of these vaccines [12], (3) inflammatory responses following vaccination can lead to reduced feed consumption [13] and (4) reversion Etomidate to toxicity may occur in incompletely inactivated bacterial toxins. Therefore, there is a need to identify Etx variants with reduced toxicity relative to wild type toxin. One approach to solving this problem is to develop recombinant vaccines based on site-directed mutants with markedly reduced toxicity. Amino acid residues Y30 and Y196 have previously been identified to play key roles in cell binding and thus, cytotoxicity of Etx [14] and [15]. Therefore, this study aimed to determine the potential of a site-directed mutant of Etx with mutations Y30A and Y196A combined, termed Y30A-Y196A, to be exploited as a recombinant vaccine against enterotoxemia. The gene encoding epsilon prototoxin, etxD, from C.

Characteristic sulfur granules on histopathology make the

Characteristic sulfur granules on histopathology make the

diagnosis of actinomycosis [5] and [6]. High suspicion is the main point for making a diagnosis, as radiological imaging is not diagnostic, as seen in this case. Management of the disease with medical drugs should be tried first. Rifampicin, isoniazid, pyrazinamide, and ethambutol are the basis of breast tuberculosis treatment [2], [3] and [4]. Surgery should be reserved for medical treatment-resistant cases. In endemic areas, tuberculosis should always be considered in the differential diagnosis of an inflammatory breast mass. “
“Conjoined twinning Small molecule library is a rare occurrence with an incidence of about 1 in 50,000 pregnancies, 60% of which result in stillbirth [1]. There is an approximate Crizotinib supplier 2–3:1 female to male predominance [1]. The classification of conjoined twins is complex, but is usually based on degree and anatomic location of the fusion [2]. Parapagus twins always share a conjoined pelvis with one or two sacrums and a single symphysis [2]. Dicephalic parapagus

twins share a common thorax and account for approximately 3.7% of all conjoined twins [1]. A 37-year-old Caucasian female, para 1–0–2–1 was referred to our department at 27 weeks gestation for evaluation of conjoined twins. The patient was a late registrant for care at 22 weeks gestation and her initial ultrasound was performed at 26 weeks gestation showing polyhydraminos and a dicephalic fetus. The patient denied any pertinent past medical or surgical history and any history of drug or toxin exposure. Both 2D and 3D ultrasound were performed on a Voluson 730 scanner

(General Electric Health Care, Milwaukee, 3-mercaptopyruvate sulfurtransferase WI) with a 4–7-MHz transducer at our institution with findings consistent with dicephalic conjoined twins with acrania (Fig. 1 and Fig. 2). Two spines were identified and appeared parallel (Fig. 3) with fusion in the thoraco-lumbar region with associated rachischisis. Cardiac imaging was difficult secondary to fetal positioning and was incomplete. There was no apparent duplication of the abdominal organs and a single 2 vessel umbilical cord was present. The largest diameter of the dicephalic presenting part was 8.8 cm, equivalent to a 35 week singleton biparietal diameter (Fig. 4). Given the findings of an assured non-viable fetal condition, the option of pregnancy termination was offered. The patient was admitted later that day and underwent an induction of labor after cardioplegia with laminaria and pitocin augmentation. She had a spontaneous vaginal delivery of a stillborn, dicephalic female fetus in cephalic presentation. The family declined chromosomal analysis, but desired a limited autopsy. Her postpartum course was uncomplicated. Permission for autopsy, excluding head, was obtained from the parents on the day of delivery. External examination was Libraries notable for a dicephalus dipus dibrachius female fetus (Fig. 5). Both fetal heads demonstrated acrania.

Patients experiencing SBP typically present with severe abdominal

Patients experiencing SBP inhibitors typically present with severe abdominal

pain, tenderness, and guarding.3 Surprisingly, our patient’s examination was inconsistent with peritonitis. Our decision to perform a cystogram first evolved after a thorough click here discussion on his presentation, history, and review of the outside-hospital CT scan raised suspicions for bladder perforation. Prompt diagnosis of SBP is important in reducing the high morbidity and mortality associated with it. Once the diagnosis is made, immediate definitive repair is warranted. Although laparoscopic repair of SBP has been described in the literature,4 multiple factors led us to perform an open repair including length of time between presentation and the time to repair and anticipation of significant amount of scarring and inflammation. Diabetic cystopathy can occur silently and early in the course of diabetes regardless of the severity of the disease.5 In the past, it has been classically described as impaired bladder sensation, increased cystometric capacity, decreased bladder contractility, impaired uroflow, and, in the later stages of the disease, increased residual urine volume. More recent studies have shown that detrusor overactivity appears PCI-32765 cost to be a more common symptom, occurring in up to 55% of patients with diabetic cystopathy. A thorough history and urodynamics are essential in making the diagnosis. Overall, the prognosis of

spontaneous bladder rupture is very poor with a mortality rate of up to 80%.4 Although the mortality is highest around the time of rupture, some patients have died months after their initial event. It is only by including rupture of the urinary bladder in the differential for patients presenting with an acute abdomen that morbidity and mortality can be reduced. “
“Xanthogranulomatous pyelonephritis (XGP) is an uncommon and distinct type of chronic infective pyelonephritis in which yellow lobulated masses diffusely replace the renal architecture. XGP predominantly affects middle-aged women, although infants and very

old men are also affected. The most common symptoms include abdominal pain, fever, Rolziracetam a palpable mass, anorexia and weight loss, a urinary tract infection resistant to antibiotics, hematuria, and dysuria. The disease is characterized by an accumulation of foamy histiocytes, macrophages with mature adipocytes, and occasional giant cells. Anemia, leukocytosis, and increased erythrocyte sedimentation rate comprise the usual laboratory findings. Its etiology remains unclear, although as many as 6 causes have been proposed: (1) urinary obstruction, (2) urinary tract infection, (3) abnormal lipid metabolism, (4) lymphatic obstruction, (5) altered immune response, and (6) vascular occlusion.1Escherichia coli and Proteus mirabilis are the most common offending microorganisms despite sterile urine in approximately one-third of patients. Two forms of XGP have been described: diffuse (83%-90%) and focal (10%-17%).

Secondly, oil-in-water emulsions improve vaccine responses agains

Secondly, oil-in-water emulsions improve vaccine responses against seasonal influenza in elderly populations, immunocompromised

patients and children [6]. They can also broaden the immunogenicity of pandemic vaccines as shown by the MF59-induced epitope spreading from HA2 to neuraminidase and HA1, thus providing cross-clade neutralization and potentially improving in vivo protection [7]. Thirdly, the safety profile of oil-in-water emulsions is well documented: MF59 and AS03 have been used successfully in over 100 million people including children. Novartis’ seasonal influenza vaccine containing MF59 is routinely and extensively used in the elderly [8], and both GSK’s AS03-adjuvanted pandemic (H1N1) 2009 influenza vaccine and Novartis’ MF59-adjuvanted pandemic (H1N1) Enzalutamide 2009 influenza vaccine were used worldwide in 2009 and 2010. It is worth noting that the technology transfer of an emulsion containing metabolizable oil and surfactant in the absence of block-copolymer from a European centre to DCVMs does not infringe any intellectual property. Access by DCVMs to this adjuvant technology would therefore be highly advantageous not only

for pandemic influenza vaccines, but could trigger benefits for further applications since oil-in-water emulsions have been widely investigated in numerous clinical trials with several subunit antigens, such as HIV, hepatitis B virus and hepatitis C virus Libraries antigens LY2157299 price [9]. In addition, the capital investment needed to produce oil-in-water

adjuvants is relatively modest and the cost of materials adds only marginally below to the cost of antigen production. The manufacturing process for oil-in-water emulsions has been described in detail [10]. The Vaccine Formulation Laboratory has established the production processes and prepared oil-in-water emulsions that meet all expected physical, chemical and biological (adjuvant activity) parameters. We are currently screening a range of raw material sources and evaluating the acceptability of the products for use in clinical-grade emulsions. This is particularly important for materials of biological origin such as squalene (prepared from shark liver) and heterogeneous surfactants such as Tween80 and Span85. In order to develop all standard operating procedures and relevant documentation for Good Manufacturing Practice (GMP) production, a collaboration has been developed with The Netherlands Vaccine Institute (NVI) in Bilthoven, The Netherlands. Bio Farma, Indonesia, a grantee of the WHO initiative to transfer the capacity to produce influenza vaccines to DCVMs, is the first technology transfer partner of the Vaccine Formulation Laboratory. The first phase of the project comprises the installation of equipment required for production and characterization of oil-in-water emulsions, the establishment of relevant standard operating procedures, training of laboratory staff, and on-site validation of the transferred processes.

, Bangalore, India) with composition of 5% fat, 21% protein, 55%

, Bangalore, India) with composition of 5% fat, 21% protein, 55% nitrogen-free extract, and 4% fiber (w/w) with adequate mineral and vitamin levels for the animals. Diet and water were provided

ad libitum. Acute toxicity studies with Mengkudu fruit extract were performed in experimental rats. Graded doses of MFE (100, 250, 500, and 1000 mg/kg body weight) were administered orally, and the animals were subsequently observed for 2 weeks. Changes in body weight, food consumption, hematological, macroscopic, and clinical biochemical findings, including the activities of enzymes, were noted. Dosage fixation studies were carried out by virtue of unequally long administration of graded doses of MFE (100, 200, 300, 400 and 500 mg/kg body weight), given to rats introduced into STZ induced hyperglycemia; it was found that the MFE shows its maximal antihyperglycemic effect at the concentration Panobinostat concentration of 300 mg/kg body weight managed Modulators orally for 30 days. Hence, the dosage was fixed at 300 mg/kg body

weight/rat/day and tracked for 30 days. Streptozotocin, 2-deoxy-2-3-(methyl-3-nitrosoureido)-d-glucopyranose, is by far the most frequently used agent (69%) in preparation of diabetic animal models for the study of multiple aspects of diabetes, and the dose required for inducing diabetes depends on the animal species, route of administration and nutritional status.13 The experimental animals were fasted overnight and diabetes was experimentally induced by intraperitoneal injection unless of STZ with a single dose of 50 mg/kg b.w./rat. STZ was dissolved in freshly prepared 0.1 M cold find more citrate buffer pH 4.5.14 Since STZ is capable of inducing fatal hypoglycemia as a result of massive pancreatic insulin release, STZ-treated rats were provided with 10% glucose solution after 6 h for the next 24 h to prevent diabetogen induced hypoglycemia.15 On 3rd day, the development and aggravation of diabetes in rats was confirmed and rats with fasting blood glucose concentration more than 250 mg/dL were selected for the experiments. The animals were divided

into four groups, comprising a minimum of six animals in each group as follows: Group 1 – control rats. The ethanolic extract of M. citrifolia fruits was subjected to preliminary phytochemical screening by standard methods. 16, 17, 18, 19 and 20 Blood glucose, hemoglobin and glycosylated hemoglobin were estimated according to the methods of Trinder,21 Drabkin and Austin,22 and Nayak and Pattabiraman23 respectively. Insulin level was measured in plasma using the sensitive rat insulin ELISA kit (Linco Research, Inc., St. Charles, MO) and the C–peptide assay was carried out by Rat C-Peptide RIA Kit. A portion of the liver and kidney tissues were dissected and washed immediately with ice-cold saline and were homogenized in 0.1 M Tris–HCl buffer (pH 7.4) for the assay of key enzymes of carbohydrate metabolism.

, 2006) Both

, 2006). Both

Wnt inhibitor perceptual and reflective attention have limited capacity, and the fact that they often trade-off suggests that they are not entirely independent. Researchers have identified some of the neural changes associated with trial-to-trial fluctuations in attention and their consequences for memory, and PRAM attempts to explain subsequent memory according to variation in either perceptual or reflective attention to different items. As described above, in studies of LTM using simple materials (e.g., words, pictures) various lateral PFC, lateral parietal, and MTL regions show greater activity for subsequently remembered than forgotten items (Blumenfeld and Ranganath, 2007, Diana et al., 2007, Kim, 2011 and Uncapher and Wagner, 2009). In contrast, greater activity for subsequently forgotten than remembered items is often found in medial PFC and medial parietal cortex (posterior cingulate, precuneus, TPJ; Kim et al., 2010, Otten and Rugg, 2001, Park et al., 2008, Turk-Browne et al., 2006 and Uncapher et al., 2011). Interestingly, these same regions are active when participants are cued to engage in reflective, self-referential, internally MS 275 oriented processing (e.g., Gusnard et al., 2001 and Ochsner et al., 2005), such as thinking about their aspirations or obligations (Johnson et al., 2006). This suggests that forgotten items in non-self-referential cognitive tasks were ones for which the participant’s attention

was momentarily diverted from the task and focused on more personal concerns. In fact,

these same anterior and posterior medial regions are spontaneously more active during “rest,” when no task at all is specified, than during many cognitive tasks (and are part of what is known as the “default network,” Raichle et al., 2001 and Buckner et al., 2008). It should be noted that when self-referential processing is relevant to a later memory task, activation in medial PFC is positively related to later memory (e.g., Macrae et al., 2004 and Kim and Johnson, 2010). Limited attention is not necessarily allocated in an all-or-none manner but may be distributed between primary (target) and other (nontarget or task-irrelevant) information (Pashler, 1998). For example, according to load theory (Lavie, 2005), the amount aminophylline of processing that nominally “unattended” stimuli receive depends on how much processing is devoted to the primary, attended target task. Difficult primary tasks (high load) consume attention; easy primary tasks (low load) do not fully consume attention, which thus spills over to process “unattended” stimuli. Consistent with load theory, increasing the perceptual difficulty of a target task can eliminate negative priming from unattended distractors (Lavie and Fox, 2000). In contextual learning tasks, increasing the difficulty of the search through attended arrays decreases implicit learning of unattended arrays (Jiang and Chun, 2001).

Most previous studies that identified clonally related neurons in

Most previous studies that identified clonally related neurons in vivo have used a retroviral labeling method (Walsh and Cepko, 1988 and Luskin et al., 1988), which labels only a handful of cells. To analyze clonally related sister cells, we used a Cre/loxP system (Magavi et al., 2012) in which all the progeny of a single cortical progenitor

(∼600 cells) were labeled. We believe that this complete labeling is important to study the relationship between orientation selectivity and lineage. First, neurons with significant responses and sharp selectivity are relatively rare—approximately 20% of mouse V1 cells (Ohki et al., 2005). By recording from ∼100 sister cells, BMS-354825 molecular weight we could measure functional properties from approximately 20 of these cells and estimate their preferred orientation distribution. If only a small number of sister cells were recorded, the probability of obtaining pairs of such neurons would be extremely low. Second, as previously reported (Ohki et al., 2005 and Kreile et al., 2011), there is often a bias in the distribution of preferred orientations in a local population of neurons in rodent visual cortex. With such

a bias, a small number selleck inhibitor of randomly chosen cells could have a similar orientation just by chance. Thus, analyzing a large number of lineage-related cells allowed us to focus on robustly tuned cells to prove that the distribution of preferred orientation of sister cells was significantly different from the other nearby neurons. Sclareol Contamination from the neuropil signal (Göbel and Helmchen, 2007) is another variable that could potentially confound the analysis of response selectivity. As described previously (Kerlin et al., 2010), the orientation tuning of the neuropil signal is similar to the average of the orientation tuning of local neurons and varies only slightly across 300 μm in the imaging field. When there is some bias in the preferred orientations of local neurons, the neuropil signal can be also tuned to the local

orientation bias and might contaminate signals from cell bodies. Since neuropil contamination becomes a larger part of the signal for weakly responsive cells, those cells may appear more similarly tuned if neuropil contamination remains. To avoid these effects of neuropil contamination, we subtracted the surrounding neuropil signal and selected only highly responsive neurons that were sharply tuned. Finally, we used pixel-based orientation maps (Figure 2C) to confirm that we used only cells with reliable responses, as sharply selective and highly responsive neurons clearly stand out in these orientation maps and have different responses than the surrounding neuropil. In some cases, we did not observe a difference in the distribution of preferred orientations between F+ and F− cells and the peaks of the distributions matched between F+ and F− cells.

The extensive reorganization in rhombomeres 3 and 5 of the Egr-2

The extensive reorganization in rhombomeres 3 and 5 of the Egr-2 null mice eliminates most RTN neurons ( Thoby-Brisson et al., 2009), but neurons outside of Egr-2 domain may compensate for the lethality caused by loss of RTN neurons. In our case, we propose that some of the RL-derived Atoh1 neurons could function collectively as a second excitatory source for the preBötC, which might stochastically reach the excitatory threshold

to allow survival of half the newborn Atoh1Phox2bCKO mice. Although the paratrigeminal neurons are anatomically intact without Atoh1, their role in respiratory control remains unknown, and we do not exclude the possibility that they modulate find more breathing in an Atoh1-dependent Onalespib ic50 manner. RL-independent and dependent Atoh1-positive neuronal subpopulations might each contribute to neonatal respiratory activity to

a similar extent. Fifty percent of newborn mice with Atoh1 deletion in the Wnt-1 lineages, which affect most of the RL-derived neurons, die within 24–36 hr of birth ( Morrison et al., 2009), which lends further support to this hypothesis. Loss of Atoh1 causes aberrant RTN neuronal migration, analogous to the consequence of loss of atonal during the development of the Drosophila dorsal cluster (DC) neurons. Atonal is expressed in the postmitotic DC neurons that innervate the optic lobes ( Hassan et al., 2000); in its absence, the DC neurons are still present, but are aberrantly positioned and show severely impaired target innervation and loss of axonal arborization. Atonal thus does not act as a classical proneural gene in the DC Astemizole neurons. Interestingly, the ability of atonal/Atoh1 to control cell positioning and target innervation is limited to the few populations where these bHLH factors are expressed postmitotically. The identity of central chemoreceptors and the mechanism by which they detect elevated pCO2 and stimulate breathing remain unclear, but

these questions are currently under intense investigation (Guyenet, 2012). The Atoh1Phox2bCKO surviving mice provide an unexpected opportunity to assess the extent to which mislocalized RTN neurons affect adult chemoresponsiveness. We observed that the Atoh1Phox2bCKO surviving mice develop a significantly impaired hypercapnic response and hypersensitivity to hypoxia, suggesting that despite the possible development of compensatory mechanisms, the Atoh1-mediated development of the RTN neurons remains a crucial step that assures proper chemosensory response throughout life. During embryonic stage, the fictive motor activity of Atoh1Phox2bCKO embryos is significantly slower than WT embryos under both baseline and pH challenge; but unlike the CCHS mouse models that lose the RTN and express Phox2b27Ala in multiple brain regions ( Dubreuil et al., 2008; Ramanantsoa et al., 2011), the pH response is virtually unchanged in the Atoh1Phox2bCKO embryos.